PubMed Health⌕ Search

Biomedical subjects

J R Wingard

Publications and source records attributed to J R Wingard.

At least 19 recordsLinked to original sources
PubMed2006

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT).

More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.

Delivery of Health Care↗
PubMed2006

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

Administration, Oral↗
PubMed2004

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease.

The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.

Anemia, Sickle Cell↗
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↗
PubMed2003

Human cord blood long-term engrafting cells are CD34+ CD38-.

There have been controversies about CD34 and CD38 expression by human cord blood (CB) stem cells. Using the newborn NOD/SCID/beta2-microglobulin-null mouse assay that we recently developed, we examined the in vivo engrafting capability of human CB cells. Almost all of the 4-5 months engrafting cells were found in CD34(+) population. The capability of secondary reconstitution was found only in the CD34(+) cells. When the CD34(+) CB cells were separated into CD38(-) and CD38(+) subpopulations and tested for engraftment, the majority of the engrafting cells were detected in the CD38(-) subpopulation. These findings are consistent with the results from studies of murine stem cells and strongly indicate that the phenotype of human CB stem cells is CD34(+) CD38(-).

ADP-ribosyl Cyclase↗
PubMed2003

Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.

Adolescent↗
PubMed2002

Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital.

Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains a principal cause of infectious mortality after bone marrow transplantation (BMT). We reviewed the medical records of 93 allogeneic and 149 autologous transplant recipients during a 20 month period, with attention to cases of proven or probable IA. No autologous transplant recipient developed IA, whereas IA was seen in 15.1% of allogeneic recipients (including two of five patients with a prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The median time to occurrence was 92 days post transplant, with no de novo cases developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk factors for the development of IA included > or = 21 days of corticosteroid therapy of >or= 1mg/kg/day and post-transplant cytomegalovirus (CMV) infection. These two risk factors were statistically linked. Our data illustrate a shift toward a later occurrence of post-transplant IA, suggesting a need for close, prolonged surveillance in the outpatient environment. The contributory role of protracted corticosteroid use is also highlighted. These data have important implications in an era of alternate donor transplants and more intense immunosuppression. Established strategies implementing newer, less toxic antifungal agents as prophylaxis in high-risk patients are needed.

Adolescent↗
PubMed2002

Mismanaging the gift of life: noncompliance in the context of adult stem cell transplantation.

In this paper, we address the issue of noncompliance with medical regimens in adult stem cell transplant patients. We review the definition, prevalence, and consequences of noncompliance and address whether or not we should alter our medical decision-making with regard to stem cell transplantation based on patient noncompliance. We discuss how the health care team should handle noncompliance issues and propose clinical guidelines for stem cell transplant programs to consider regarding evaluation and management of medical compliance.

Adult↗
PubMed2002

Treatment of refractory acute leukemia with timed sequential chemotherapy using topotecan followed by etoposide + mitoxantrone (T-EM) and correlation with topoisomerase II levels.

A phase I/II clinical study evaluated 17 patients with refractory/recurrent acute leukemia treated with 1.5 mg/m2/day topotecan on days 1-3 followed by etoposide (100 mg/m2/day)+mitoxantrone (10 mg/m2/day) on days 4, 5 and 9, 10. Timed sequential chemotherapy using the topoisomerase I-inhibitor topotecan before the topoisomerase II-inhibitors, etoposide+mitoxantrone (T-EM) treatment is proposed to induce topoisomerase II protein levels and potentiate the cytotoxic activity of the topoisomerase II-directed drugs. Fourteen patients had refractory and three had recurrent acute leukemia. The majority of patients were heavily pre-treated with greater than three re-induction chemotherapy regimens. Ten patients responded to T-EM treatment (59%). Four of seventeen (24%) had a complete remission and one had a partial remission. Four additional patients (24%) who scored complete leukemia clearance had no evidence of disease with complete white and red blood cell recovery but with platelet counts less than 100,000. The lack of platelet recovery in one patient having a partial response was scored as a partial leukemia clearance. The toxicity profile included major non-hematological toxicity including grade 3 mucositis (29%) and neutropenic fever (65%). Paired measurements of intracellular levels of topoisomerase II isoforms alpha and beta in leukemia blast cells (bone marrow) collected before (day 0) and after topotecan treatment (day 4) showed that a relative increase of topoisomerase IIalpha (Topo IIalpha) > or = 40% strongly correlated with response after T-EM treatment. Increased Topo IIalpha levels also corresponded to increased DNA fragmentation. Two patients who had an increase of Topo IIalpha of 20-25% had either a PR or PLC while patients with a < 10% increase showed no response to T-EM treatment. We conclude that timed sequential chemotherapy using topotecan followed by etoposide+mitoxantrone is an effective regimen for patients with refractory acute leukemia, and demonstrate Topo IIalpha protein level increases after topotecan treatment.

Acute Disease↗
PubMed2002

GM-CSF versus G-CSF: engraftment characteristics, resource utilization, and cost following autologous PBSC transplantation.

BACKGROUND: G-CSF and GM-CSF have both been shown to decrease the time to hematopoietic recovery when administered after autologous BM or peripheral stem cell re-infusion. However, few studies have compared G-CSF and GM-CSF to determine which is the preferred myeloid growth factor. METHODS: This study compares a prospectively accrued cohort of 22 patients receiving GM-CSF with a historical cohort of patients who received G-CSF commencing Day + 6 after autologous PBSC transplantation. Patients were matched based on disease type and stage, CD34(+) cell dose/kg, conditioning regimen, and prior treatment. Time to myeloid engraftment, growth factor utilization, antibiotic utilization, fever incidence, and cost were compared. RESULTS: The median time to neutrophil and platelet engraftment was similar in the two groups (ANC > 500 /mm(3), GM-CSF 12 versus G-CSF 11, P = 0.69). There was a trend towards more days of temperature > 38.0 masculine C (six versus three, P = 0.05) and febrile neutropenia (three versus two, P = 0.06) in the GM-CSF arm. There was a trend towards increased use of i.v. antibiotics in the GM-CSF cohort (7.6 days versus 5.5 days, P = 0.06). More chest X-rays (1.5 versus 1.0, P = 0.03) were ordered, and more blood cultures drawn (4.2 versus 2.7, P = 0.05) as part of fever evaluation in the group treated with GM-CSF. Resource utilization based on actual wholesale pricing (AWP) favored the G-CSF cohort. Applying a sensitivity analysis, GM-CSF became cost-effective when priced below $94 per 250 micro g, despite greater resource utilization. DISCUSSION: This study suggests that engraftment characteristics are similar with GM-CSF and G-CSF following PBSC transplantation. Resource utilization for fever treatment and evaluation may be greater with GM-CSF. Determination of which agent is more cost-effective depends on institutional acquisition costs.

Adolescent↗
PubMed2001

Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients.

Bacteria remain an important cause of infection in bone marrow transplants. To examine shifts in the etiology and susceptibility of bacterial isolates from transplants, we reviewed the incidence and susceptibility of blood isolates during a 7-year period. The infection rate fell dramatically during this time. Gram-positive organisms were isolated more often than gram-negative organisms, but the trend is reversing. Streptococci surpassed staphylococci for 5 years as the leading pathogen. Increasing resistance to penicillin, ciprofloxacin, and imipenem was noted in Streptococcus species. With the exception of type 1 beta-lactamase-producing bacteria and Pseudomonas aeruginosa, gram-negative isolates remained overall susceptible to ceftazidime. Increased antibiotic prophylaxis coincided with the reduction in percentage of infected patients and increase in resistance to beta-lactam antibiotics. Mortality attributed to bacteremia was low except for infections caused by P. aeruginosa and the Enterobacter, Serratia, Citrobacter group. There was no mortality attributable to gram-positive organisms such as Staphylococcus aureus and viridans streptococci.

Adolescent↗
PubMed2001

Infections following hematopoietic stem cell transplantation.

Numerous advances have been made in the management of infection in HSCT recipients. With increasing knowledge the authors are able to prevent several serious infections from occurring, and reduce the severity of infections once they occur. Despite these advances, several previously unrecognized pathogens have emerged and pose risks to this population. Ongoing surveillance and reporting of atypical infections are warranted. Transplant and infectious disease clinicians alike must be vigilant to the shifts in infectious syndromes as a consequence of various prophylaxis and preemptive strategies, and be ready to modify empiric strategies to meet the changing microbiologic milieu. As we increase our understanding of the HSCT process, and use the immune system rather than relying on high-dose chemotherapy, the authors are likely to reduce toxicities and improve patient outcomes.

Bacterial Infections↗
PubMed2001

Engraftment syndrome in breast cancer patients after stem cell transplantation is associated with poor long-term survival.

An autoaggression graft-versus-host (GVHD)-like syndrome or engraftment syndrome (ES) presenting with skin rash, fever, and other clinical findings can accompany the early phase of engraftment after autologous peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation. Because ES was suggested to be analogous to GVHD, we have investigated whether ES was associated with any graft-versus-tumor effect that would affect disease progression and survival in breast cancer patients. Eighty-five consecutive patients who received BM/PBSC transplantation for breast cancer (stages II-IV) between July 1991 and July 1997 with minimum 2-year follow-up were studied. Median follow-up time was 892 days (range, 106-2913 days). Thirty-three patients (39%) developed ES. The incidence of relapse/progressive disease for the whole cohort was 61% and was similar in patients who developed ES compared with those who did not. However, there was an increased rate of mortality observed among the patients who had developed ES versus those who had not, although it was statistically not significant, (52% versus 31%, respectively; log rank, P = .08). Increased mortality rates due to disease progression were seen in all patients with ES regardless of their disease stage. In relapsed patients, median survival time after transplantation was 586 days for those with ES versus 847 days for those without ES, and the mortality rate was 85% (17/20) versus 51% (16/31) (P = .008) for those with or without ES, respectively. Visceral (lung, liver, brain, adrenal) or multiple-site relapses were observed in 85% of patients with ES versus 52% without ES (P = .01). In conclusion, whereas there was no effect of ES on relapse rate, a surprisingly significant increase in disease-related mortality rates among relapsed breast cancer patients with ES was found. Thus, patients with ES should be considered for close follow-up and further therapy posttransplantation.

Adult↗
PubMed2001

Treatment of post-transplant lymphoproliferative disease with induction chemotherapy followed by haploidentical peripheral blood stem cell transplantation and Rituximab.

Management of monoclonal lymphoproliferative disease following stem cell transplantation is difficult and previous attempts to eradicate tumor using chemotherapy or radiation therapy alone have not been successful. We report successful early eradication of an EBV negative, B cell non-Hodgkin's lymphoma in a child who received a T cell-depleted, maternal haploidentical bone marrow transplant for severe combined immunodeficiency disease. Our treatment strategy involved combining conventional induction chemotherapy with re-transplantation using the paternal donor as a source of peripheral blood stem cells, followed by treatment with anti-CD 20 monoclonal antibody (Rituximab). This strategy exploits the potential graft-versus-tumor activity of the mature T cells in the graft, while providing a source of stem cells to confer long-term immune function. The administration of Rituximab in the early post-transplant course may provide additional anti-tumor activity without affecting the new stem cell compartment.

Antibodies, Monoclonal↗
PubMed2001

Monitoring vital signs in a bone marrow transplant unit: are they needed in the middle of the night?

Monitoring vital signs (VS) is a routine procedure in bone marrow transplant (BMT) units, but such monitoring can interfere with sleep. We hypothesized that middle of the night (MON) monitoring may not be needed in all patients. Charts of 20 consecutive patients who underwent BMT were reviewed for MON monitoring to determine the frequency with which monitoring resulted in a nursing intervention, call to the physician or change in treatment by the physician. Charts were also reviewed for day time events, which could predict the need for monitoring at night. MON monitoring was done on 457 of the 543 nights evaluated, 148 nursing interventions were performed during these 457 nights (32%) of which only 20 (4%) were the result of monitoring VS. In five instances, the nurse called the physician as a result of monitoring VS and in three of these five instances, the treatment was changed. The only day time event that was significantly associated was fever (P = 0.0002). There was also a trend for CNS events (P = 0.057) to be associated with MON intervention. Larger, prospective studies need to be done to accurately identify day time risk factors that can predict the need for night time monitoring.

Adult↗
PubMed2001

Gastroparesis following bone marrow transplantation.

Patients often develop nausea, vomiting and bloating after bone marrow transplantation (BMT). These symptoms may interfere with nutrition and the ability to take oral medications. Gastroparesis is a recognized cause of these symptoms in non-transplant patients but less is known about patients who undergo BMT. Between January 1996 and March 1997, a total of 151 patients underwent BMT. Eighteen patients (12%) developed persistent symptoms suggestive of gastroparesis (persistent nausea, vomiting or bloating). Scintigraphic gastric emptying studies were performed to assess for gastroparesis. Prokinetic agents were administered at the time of study. The records on these patients were compared with those of all other patients undergoing BMT during the same time period without these symptoms. Nine patients who demonstrated delayed gastric emptying were further evaluated with esophagastroduodenoscopy and biopsy. Biopsy samples were reviewed for evidence of graft-versus-host disease (GVHD). Fourteen of 18 patients demonstrated delayed gastric emptying and most responded to prokinetic agents given at the time of study. Age, conditioning regimen, cytomegalovirus antigenemia and acute GVHD did not appear to be associated with the development of gastroparesis. Allogeneic BMT recipients were at higher risk than autologous BMT patients (26% vs 0%, P < 0.0001). of allogeneic bmt recipients, there was a nonsignificant trend of patients receiving tacrolimus to be less likely to experience gastroparesis than those receiving cyclosporine (27% vs 48%, P = 0.08). For the nine patients undergoing upper endoscopy, GVHD on gastric biopsy was an uncommon finding and was mild when present. Gastroparesis appears to be a common cause of nausea, vomiting and bloating following allogeneic BMT. This may occur less often with tacrolimus than cyclosporine because of the former agent's prokinetic properties. Patients usually respond to prokinetic drugs at the time of scintigraphy. GVHD and CMV infection do not appear to be major contributing factors.

Adult↗
PubMed2001

A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation.

Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease (GVHD) and infections, but the minimally effective dose has not been established. In this multicenter, randomized, double-blind trial, patients undergoing allogeneic marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500 mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days and then monthly until 1 year after transplant. Six hundred and eighteen patients were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of 206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344). Among patients with unrelated marrow donors, a higher dose of intravenous immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The incidences of chronic GVHD, infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin. The dose of intravenous immunoglobulin also had no effect on the types of infection, relapse of hematological malignancy or survival. Except for more frequent chills (P = 0.007) and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin, adverse events were similar for all three doses. These results suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants. These results should be considered when designing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection.

Adolescent↗