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J E Wagner

Publications and source records attributed to J E Wagner.

At least 73 records · Page 4Linked to original sources
PubMed1995

Density separation of umbilical cord blood and recovery of hemopoietic progenitor cells: implications for cord blood banking.

Umbilical cord blood (CB) has been evaluated as a potential source of hematopoietic stem cells suitable for clinical use in the transplantation setting. Previous reports have documented a significant loss of progenitor cells by any manipulation other than cryopreservation. We have evaluated the feasibility of fractionating and cryopreserving CB samples with minimal loss of progenitor cells. We have compared various separation procedures based on different density gradients in the attempt to obtain the highest depletion of red blood cells (RBC) while maintaining the highest recovery of progenitor cells. We compared three different densities of Percoll (1.069 g/ml, 1.077 g/ml, 1.084 g/ml), sedimentation over poligeline (Emagel ) and sedimentation over poligeline followed by separation over Ficoll/Hypaque (F/H). Separated samples (n = 25) were analyzed for recovery of CD34+ cells and progenitor cells (CFU-GEMM, BFU-E, CFU-GM). Separation by sedimentation over poligeline followed by F/H allowed the highest depletion of RBC (hematocrit of the final cellular suspension 0.4 +/- 0.1%) while maintaining high recovery of CD34+ cells (85.3 +/- 5.6%) and total recovery for CFU-GEMM, BFU-E and CFU-GM. After cryopreservation, recovery of clonogenic progenitors was 82% for CFU-GEMM, 94% for BFU-E, 82% for CFU-GM and 90% for colony-forming units (CFUs) after five weeks of long-term culture (LTC). We further evaluated the effect of stem cell factor (SCF) on the in vitro growth of hemopoietic progenitors and on replating efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1995

Umbilical cord blood transplantation.

Interest in umbilical cord blood as an alternative source of hematopoietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor; there is no need for general anesthesia or blood replacement, and the procedure causes no discomfort. Whether cord blood lymphocytes are as likely to cause GVHD as lymphocytes from older individuals is unknown. Current clinical experience would suggest that the incidence may be low. Few of the patients who have thus far received umbilical cord blood, including recipients of HLA-disparate grafts, have developed clinically significant GVHD. These results and associated laboratory findings pose intriguing possibilities for the future of umbilical cord blood stem cells in the setting of unrelated-donor transplantation. With the marked incidence of Grade 2 to 4 acute GVHD that is currently observed after unrelated-donor bone marrow transplantation, a reduction in incidence or severity would be a major advance in this field. In the setting of autologous marrow transplantation, there are other intriguing possibilities; for example, cord blood may be an optimal source of pluripotential stem cells for use in gene therapy. As detailed in Broxmeyer's review, the large-scale collection and storage of cord blood stem cells is no longer just a concept; it has become a reality. Pilot programs for the banking of unrelated-donor umbilical cord blood have already begun in the United States and Europe.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗
PubMed1994

Umbilical cord blood transplantation: overview of the clinical experience.

In an attempt to reduce the morbidity and mortality associated with allogeneic bone marrow transplantation, clinical investigators in Asia, Australia, Europe, and North America have evaluated umbilical cord and placental blood as an alternate source of hematopoietic stem and progenitor cells for transplantation. To date, umbilical cord blood has been used to reconstitute hematopoiesis in 34 patients with a variety of malignant and nonmalignant diseases treated with myeloablative therapy. Although the median number of nucleated cells infused was only 4.0 x 10(7)/kg of the recipient's body weight (range, 0.1-33.0 x 10(7)), the median time to hematopoietic recovery was 25.0 days for neutrophils (i.e., absolute neutrophil count > 500/microL, range, 12-46) and 43.5 days for platelets (i.e., absolute platelet count > 50,000/microL, range: 15-105+). Except in three patients who failed to demonstrate any evidence of hematopoietic recovery and one patient who had prompt autologous recovery, engraftment of donor cells was documented in all patients, including recipients of HLA-mismatched grafts. Of 23 evaluable patients with HLA-identical or HLA-1 antigen-mismatched donors, none had grade 2-4 acute graft vs. host disease (GVHD). In summary, these data suggest that umbilical cord blood is an acceptable source of transplantable hematopoietic stem cells, at least in recipients < 40 kg and that the risk of acute GVHD is low.

Adolescent↗
PubMed1994

Lichenoid chronic graft-vs-host disease occurring in a dermatomal distribution.

BACKGROUND: Chronic graft-vs-host disease (GVHD) is a late complication of allogeneic bone marrow transplantation and is associated with high morbidity and mortality. While the pathogenesis of chronic GVHD is not fully understood, several observations and studies suggest that viral infections may play a role. We describe two patients who developed linear lichenoid chronic GVHD. The dermatomal distribution of their lesions suggests an association with herpes zoster virus infection. OBSERVATIONS: Two allogeneic bone marrow transplantation patients developed violaceous papules in a dermatomal distribution. Histologic examination of these lesions revealed dyskeratosis, vacuolar changes in the basal layer, and a mild perivascular and interstitial infiltrate, diagnostic of lichenoid chronic GVHD. CONCLUSIONS: The linear distribution of our patients' lichenoid chronic GVHD is unique and may represent an association with herpes zoster virus infection, providing further support for a role for viral infections in the pathogenesis of chronic GVHD.

Adult↗
PubMed1993

Umbilical cord blood stem cell transplantation: current status and future prospects (1992).

Human umbilical cord and placental blood provide a rich source of hematopoietic stem cells. On the basis of this finding, umbilical cord blood stem cells (CBSCs) have been used to reconstitute hematopoiesis in children with malignant and nonmalignant diseases after treatment with myeloablative doses of chemoradiotherapy. Early results have been sufficiently encouraging to (1) embark on large-scale banking of cord blood for purposes of future autologous and allogeneic stem cell transplantation, (2) warrant studies of in vitro CBSC expansion, (3) initiate investigations of retroviral-mediated gene transfer into CBSCs for future gene therapy trials, and (4) justify the development of CBSC study groups in both Europe and the United States. This review briefly summarizes what is known about CBSCs in transplantation as well as potential future directions for this unique source of hematopoietic stem cells.

Blood Banks↗
PubMed1993

Umbilical cord and placental blood transplantation: analysis of the clinical results.

In an attempt to reduce the complications associated with allogeneic bone marrow transplantation (BMT), a number of investigators in Europe, Australia, and the United States have evaluated umbilical cord and placental blood as a source of hematopoietic stem cells for transplantation. On the basis of prior laboratory investigations, cryopreserved umbilical cord blood stem cells (CBSC) were used in the treatment of 15 patients with malignant (n = 8) and nonmalignant (n = 7) disorders. The median recipient age was 4 years (range: 2-11 years). Thirteen donor-recipient pairs were HLA-identical and two were HLA-mismatched. While eight donor-recipient pairs were ABO-incompatible (6 major/2 minor), none of these 8 cord blood grafts was erythrocyte or plasma depleted prior to cryopreservation. After treatment with myeloablative doses of chem(radio)therapy, 14 of 15 patients received graft-versus-host disease prophylaxis consisting of cyclosporin A alone or in combination with other immunosuppressive agents. The mean volume of umbilical cord blood collected was 126.4 ml (range: 64-282 ml); the mean number of nucleated cells in the graft was 1.39 x 10(9). Hematopoietic recovery occurred in 13 of 15 patients with a median time to ANC > or = 500/microliters of 28.5 days. Mild cutaneous acute graft-versus-host disease was diagnosed in 5 of 11 evaluable patients with HLA-identical donors and in 1 evaluable patient with an HLA-mismatched donor; no patient had significant disease by report. The median follow-up of the 9 event-free survivors is 1.9 years (range: 0.3-4.2 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Umbilical cord blood stem cell transplantation.

PURPOSE: Human umbilical cord blood is a new source of hematopoietic stem cells. PATIENTS AND METHODS: On the basis of prior laboratory investigations in an animal model and subsequent in vitro studies of human hematopoietic progenitors, umbilical cord blood was used to reconstitute hematopoiesis in a patient with Fanconi anemia in 1988. As a result of this first success, umbilical cord blood has been used in the treatment of 15 children with a variety of malignant and nonmalignant diseases, including acute and chronic leukemia, lymphoma, neuroblastoma, Fanconi anemia, aplastic anemia, Hunter syndrome, and congenital immunodeficiency. RESULTS AND CONCLUSIONS: This review summarizes the brief history and potential future applications of cord blood stem cells (CBSCs) in transplantation.

Animals↗
PubMed1992

Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation.

Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.

Bone Marrow Transplantation↗
PubMed1992

Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.

The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.

Base Sequence↗
PubMed1992

Umbilical cord and placental blood hematopoietic stem cells: collection, cryopreservation, and storage.

Human umbilical cord and placental blood is a rich source of hematopoietic stem cells that can be used to reconstitute hematopoiesis after intensive myeloablative therapy. Therefore, it has become necessary to develop techniques for (i) collecting large volumes of umbilical cord aseptically, (ii) optimizing the yield of viable cells after cryopreservation and thawing, and (iii) minimizing the risk of maternal T-cell contamination. Our protocol for the collection, cryopreservation, storage, and transport of human umbilical cord and placental blood is described in detail.

Blood Preservation↗
PubMed1992

Prevention of graft failure by cyclosporine in rats receiving lymphocyte-depleted MHC-mismatched bone marrow.

Graft failure in recipients of lymphocyte-depleted allogeneic bone marrow transplants is a major limitation to the success of this approach for preventing acute graft-versus-host disease. In a rat BMT model, we evaluated the effect of cyclosporine dose and schedule of administration on the engraftment of MHC-mismatched bone marrow. Lewis Brown-Norway rat recipients were prepared with myeloablative doses of busulfan (day -2) and cyclophosphamide (day -1) and then transplanted with MHC-mismatched ACI rat BM (day 0) that had been depleted of lymphocytes by counterflow centrifugal elutriation. Beginning on day -1, LBN rats received variable doses of CsA (i.e., 12.5, 10.0, 7.5, 5.0, 2.5, 0.0 mg/kg/day) for various lengths of time after BMT (i.e., 7, 14, 21, or 28 days). While all rats receiving high-dose CsA (i.e., 12.5 or 10.0 mg/kg/day) for 28 days had stable donor-derived hematopoietic reconstitution, rats receiving a daily dose of CsA less than or equal to 5.0 mg/kg/day or CsA for less than or equal to 21 days had a high incidence of graft failure. The data argue that (1) graft resistance can be suppressed by CsA and (2) the effectiveness of CsA for securing engraftment is dependent upon both dose and duration of treatment.

Animals↗
PubMed1992

Bone marrow transplantation of chronic myelogenous leukemia in chronic phase: evaluation of risks and benefits.

PURPOSE: Allogeneic bone marrow transplantation (BMT) is an option for some patients with chronic myelogenous leukemia (CML). We retrospectively evaluated the effect of various risk factors observed at diagnosis and at transplantation on survival, event-free survival (EFS), and relapse after BMT. PATIENTS AND METHODS: Seventy-nine patients with CML in chronic phase (CP) were treated with cyclophosphamide and total body irradiation followed by BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CsA) in most instances or CsA plus the use of lymphocyte-depleted bone marrow (BM). RESULTS: Survival at 4.5 years was 52%. Stratified by age and GVHD prophylaxis, the actuarial survival was 65% (95% confidence interval [CI], 47% to 78%) in patients aged less than 30 years receiving unmanipulated BM, 33% (95% CI, 12% to 56%) in patients greater than or equal to 30 years old receiving unmanipulated BM, and 38% (95% CI, 14% to 63%) in patients greater than or equal to 30 years old receiving lymphocyte-depleted BM. In univariate analysis, patient age (greater than or equal to 30 years) and the use of lymphocyte-depleted BM negatively influenced EFS. When stratified by age and GVHD prophylaxis, however, ABO incompatibility, cytomegalovirus (CMV) seropositivity, and chronic GVHD significantly reduced the probability of EFS. Factors that have been associated with early death in nontransplanted patients (ie, sex, spleen size, blast and platelet counts at presentation) were not predictive of long-term survival outcome after BMT. CONCLUSIONS: The data suggest that (1) BMT should be offered early after diagnosis to all patients with CML in CP who have compatible sibling donors regardless of prognostic factors at presentation, (2) GVHD remains the principal cause of mortality after BMT in patients receiving CsA, and (3) T-cell depletion by the physical separation method of counterflow elutriation (CE) is associated with a significant risk of relapse.

Adolescent↗
PubMed1992

Relapse of leukemia after bone marrow transplantation: effect of second myeloablative therapy.

Twenty-three patients with recurrent leukemia after bone marrow transplantation (BMT) underwent a second myeloablative therapy followed by second transplant between June 1977 and April 1991. Patients had either acute lymphocytic leukemia (n = 4), acute myelogenous leukemia (n = 7) or chronic myelogenous leukemia (n = 12). The median age was 29 years and the median interval between first and second BMT was 22.6 months. The second preparative therapy consisted of cyclophosphamide (200 mg/kg) and total body irradiation (1200 cGy) in nine patients and busulfan (16 mg/kg) and cyclophosphamide (120-200 mg/kg) with or without etoposide (30-60 mg/kg) in 14 patients. The same sibling donor (three syngeneic, 20 allogeneic) was used for both transplants. All patients demonstrated prompt neutrophil recovery (median 21 days) with donor-derived hematopoiesis documented in 16 of 16 evaluable patients. With a median follow-up of 24 months after second BMT, the survival, event-free survival and probability of remaining in remission at 26 months are 47%, 38% and 76% respectively. Outcome was best in patients with chronic myelogenous leukemia (7/12 survivors) and worst in patients with acute leukemia (2/11 survivors). Thus, the data would suggest that (1) selected patients with recurrent leukemia after BMT can still be cured with myeloablative therapy and second BMT, and (2) further improvements in outcome will be dependent upon the reduction of regimen-related toxicity.

Adolescent↗
PubMed1991

Treatment of Trichophyton mentagrophytes infection in rabbits.

Copper sulfate and a metastabilized chlorous acid/chlorine dioxide (MECA) compound were evaluated for efficacy in treating Trichophyton mentagrophytes infection in rabbits. Forty rabbits naturally infected with T mentagrophytes were allotted to 5 treatment groups: nontreated control, sham dip, 1% copper sulfate dip, MECA dip, and MECA spray. Results of lesion culture, regression of gross lesions, and histopathologic findings were documented. Copper sulfate and MECA were effective in treating clinical dermatophytosis and in decreasing T mentagrophytes carrier status in rabbits.

Administration, Topical↗