Search PubMed⌕ Search

Biomedical subjects

D Adkins

Publications and source records attributed to D Adkins.

At least 37 records · Page 2Linked to original sources

Tularemia--an unusual cause of a solitary pulmonary nodule in the post-transplant setting.

We report a case of tularemia presenting as a solitary pulmonary nodule following syngeneic PBSC transplant. Seven months after undergoing a syngeneic PBSC transplant for AML, our patient presented with fever without localizing signs. Chest X-ray revealed a solitary pulmonary nodule. Culture of a CT guided needle aspiration revealed Francisella tularensis. The patient was successfully treated with ciprofloxacin. His fever resolved and clearance of the nodule was documented on a CT scan 2 months after diagnosis and initiation of treatment. To our knowledge, this is the only reported case of tularemia occurring in the post-transplant setting. The possible relationship between transplant-induced immune dysfunction and the occurrence of this rare infection is discussed.

Anti-Infective Agents↗

Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients: graft-versus-host disease and transplant-related mortality.

PURPOSE: To determine the risks of graft-versus-host disease (GVHD) and transplant-related mortality after allogeneic peripheral-blood stem-cell (PBSC) transplantation. PATIENTS AND METHODS: Between December 1994 and July 1996, 50 consecutive patients with high-risk hematologic malignancies in first remission or relapse received high-dose therapy followed by transplantation of granulocyte colony-stimulating factor-mobilized, allogeneic PBSCs collected from HLA-identical siblings. GVHD prophylaxis included cyclosporine and corticosteroids. RESULTS: As of April 1, 1998, 18 patients (36%+/-13%) survived with a median follow-up period of 767 days (range, 602 to 1,127 days). The actuarial probability of grades 2-4 acute GVHD was 0.37+/-0.14 (95% confidence interval). Of 36 assessable patients, 26 (72%+/-15%) developed chronic GVHD. The actuarial probability of chronic GVHD 2 years after transplantation was 0.87+/-0.15. Of 14 progression-free survivors, 11 (79%+/-22%) have active, chronic GVHD. All 11 patients require ongoing immunosuppression, and nearly two thirds have extensive disease. Thirteen patients died as a result of transplant-related mortality (26%+/-12%), six (12%) before and seven (14%) after day +100. CONCLUSION: We observed a high risk of chronic GVHD after allogeneic PBSC transplantation, which compromised the performance status of most long-term survivors and resulted in a relatively high risk of late transplant-related mortality. Approximately 75% of transplant-related deaths were associated with GVHD; thus, reduction in transplant-related mortality after allogeneic PBSC transplantation will require more effective strategies for the prophylaxis and/or treatment of GVHD.

Adolescent↗

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.

Adult↗

Hydroxyethylstarch sedimentation by gravity ex vivo for red cell reduction of granulocyte apheresis components.

BACKGROUND: When selecting only leukocyte compatible donors, the requirement of ABO compatibility limits the investigation and application of granulocyte transfusion therapy by reducing the pool of potential donors. Ex vivo hetastarch (HES) sedimentation was evaluated as a method of red blood cell (RBC) reduction of granulocyte components. The objective was to determine if this procedure consistently resulted in reduction of component packed RBC (PRBC) volume to < 5 ml, the range acceptable for infusion of ABO incompatible blood components based on guidelines set forth by the American Association of Blood Banks (AABB). STUDY DESIGN AND METHODS: HLA-matched, ABO-compatible sibling marrow donors were selected to donate granulocyte components, which were transfused into the allogeneic bone marrow transplant (BMT) recipient as prophylaxis against infection. Three granulocyte components were collected from each of 5 donors receiving G-CSF (daily x 5). Leukapheresis (LA) began 1 day after the first G-CSF dose (Day 1), and was repeated on Days 3 and 5. LA were performed using a continuous-flow blood cell separator, with 7L blood processed during each procedure. RBC sedimentation was facilitated by administration of a 6% HES solution to the donor line. The 5 granulocyte components collected on Day 1 were not manipulated after collection. The 10 components collected on Days 3 and 5 were manipulated by ex vivo gravity sedimentation for 60 minutes followed by transfer of the buffy coat (red cell poor [RCP] fraction) to a transfer bag with residual RBCs retained in the collection bag (red cell rich [RCR] fraction). The PRBC volume and cellular composition of the components and fractions were determined. RESULTS: When data for the 10 manipulated components were combined, the fraction of the components with < 5 ml PRBC was 0.4 in the RCP and 0.1 in the RCR fractions. All unmanipulated components contained > 5 ml PRBC. The mean PRBC volume (ml) of the RCP and RCR fractions were 6.3 and 16.4, respectively (P = .06). The mean number of RBC (x10(11)) in the RCP and the RCR fractions were .41 and 1.73, respectively (P = .03). The average proportion of cells in the manipulated components lost to the RCR fraction was 19.2% of granulocytes and 18.6% of platelets. CONCLUSION: Ex vivo HES sedimentation, as performed, significantly reduced the number of RBCs from granulocyte components, but did not consistently result in PRBC volumes in the RCP fraction within the range acceptable for infusion of ABO incompatible blood components based on the AABB guidelines. Moreover, significant numbers of granulocytes were lost to the RCR fraction.

Erythrocytes↗

Treatment of resistant mantle cell lymphoma with allogeneic bone marrow transplantation.

Conventional approaches to the treatment of recurrent mantle cell lymphoma (MCL) yield unsatisfactory results. We describe a patient with recurrent MCL in leukemic phase refractory to chemotherapy who was successfully treated with allogeneic bone marrow transplantation. At last follow-up 1 year post-transplant, the patient was in complete remission and had limited chronic graft-versus-host disease.

Bone Marrow Transplantation↗

Granulocyte collection efficiency and yield are enhanced by the use of a higher interface offset during apheresis of donors given granulocyte-colony-stimulating factor.

BACKGROUND: Trials evaluating granulocyte transfusions for therapy of febrile neutropenia demonstrated mixed clinical results, which may in part be due to the low neutrophil cell dose of the transfused components. To optimize the latter variable, the effect of various interface offset (IO) settings during apheresis on granulocyte collection efficiency (GCE) and yield was determined in normal donors given granulocyte-colony-stimulating factor (G-CSF). STUDY DESIGN AND METHODS: Seventeen donors underwent 44 granulocyte collections performed with a continuous-flow blood cell separator with hetastarch infusion after stimulation with G-CSF (5 micrograms/kg/day). Apheresis was performed alternatively using one of three IO settings: IO = 15 (Group 1, n = 16), IO = 25 (Group 2, n = 12), and IO = 35 (Group 3, n = 13). The GCE and yield and changes in donor platelet count, hematocrit (Hct), and red cell (RBC) volume of the components were compared among the three groups. RESULTS: The mean GCE was greater (p = 0.006) during apheresis at an IO setting of 35 (60 +/- 12%) than at an IO setting of 15 (40 +/- 17%). The mean granulocyte yield (x10(10) per procedure was 10.8 +/- 2.95 at an IO setting of 35 and 7.73 +/- 4.02 at an IO setting of 15 (p = 0.08). In a multivariate linear regression model, factors independently associated with granulocyte yield were the absolute granulocyte count (r = 0.73, p < 0.001) and blood volume of the donor (r = 0.54, p = 0.001) before the procedure and the use of an IO setting of 35 (r = 0.50, p = 0.002). There was no significant difference among the three groups in the decrement in donor platelet count or Hct with apheresis, although the mean RBC volume was greater in Group 3. CONCLUSION: Granulocyte apheresis at an IO setting of 35 rather than 15 resulted in a significant increase in the GCE. The use of an IO setting of 35 during apheresis was an independent factor associated with granulocyte yield in the multivariate model. Donor safety was not compromised by collecting granulocytes at the higher IO setting.

Adult↗

Protect yourself.

Explore the source record for details and available documents.

Adaptation, Psychological↗

Indium-labeled white blood cells apheresed from donors receiving G-CSF localize to sites of inflammation when infused into allogeneic bone marrow transplant recipients.

G-CSF administration to normal donors results in granulocyte apheresis yields generally greater than those observed with other neutrophil mobilizing agents. In vitro, neutrophils cultured with G-CSF exhibit prolonged survival; however, the random migration of neutrophils exposed to this agent is inhibited. Although transfused neutrophils mobilized with agents other than G-CSF migrate to sites of inflammation or infection in vivo, this has yet to be demonstrated with infusion of G-CSF-mobilized neutrophils into neutropenic human subjects. Five neutropenic allogeneic bone marrow transplant (BMT) patients each received a fresh infusion of G-CSF-mobilized indium-labeled irradiated white blood cells (WBC) apheresed from HLA-matched normal donors on day +5 post-transplant. Localization of activity on delayed scintigraphic images of indium-labeled WBC scans to sites of tissue damage (oral/nasopharynx in two patients with mucositis and terminal ileum/cecum in one with diarrhea) occurred, and supports the hypothesis that G-CSF-mobilized HLA-matched donor neutrophils which have been irradiated are functional after infusion into neutropenic recipients.

Adolescent↗

Resolution of invasive central nervous system aspergillosis in a transplant recipient.

Central nervous system (CNS) aspergillosis carries a uniformly poor prognosis in bone marrow transplant recipients. Amphotericin B can be bound to lipid carriers leading to improvement of its therapeutic index. We describe the successful medical management of CNS aspergillosis in an allogeneic bone marrow transplant patient with administration of Amphotericin B Lipid Complex.

Adolescent↗

Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation.

Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic malignancies. Since only a fraction of these patients are cured, physicians are more frequently faced with the dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation (alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect. For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after ASCT. We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML (n = 6) who underwent alloBMT after failing an ASCT. The median age was 30 (17-41) years and the interval from ASCT to alloBMT was 10.5 (2-25) months. Seventeen patients died between 0.3 to 11 months (median 2.0) after alloBMT, all due to BMT-related toxicities. Three patients remain alive and free of disease at 1.1, 1.2 and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute GVHD. Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of grade II-IV acute GVHD. Alternative treatments with salvage chemotherapy, radiation or investigational approaches should be considered in patients who relapse after ASCT.

Adolescent↗

Randomized comparison of G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells: effects on hematopoietic recovery after high-dose chemotherapy.

Fifty patients with either lymphoid or selected solid tumor malignancies were apheresed an identical number of times for PBSC collection after being randomized to receive either G-CSF 10 microg/kg/day alone (arm I), or G-CSF at the same dose with GM-CSF 5 microg/kg/day (arm II). Growth factor(s) was/were given as the stem cell mobilizing agent for 5 days before the start of PBSC collection, and were continued throughout the 4 days of apheresis. Aspiration and cryopreservation of autologous bone marrow occurred on day 3 or 4 of growth factor(s). Thirty-one of 50 patients received one cycle only at time of evaluation, and 19 patients received two cycles of HDCT, each supported with PBSC with or without autologous bone marrow. No patients received growth factors post-autologous stem cell transplant, unless the absolute neutrophils count (ANC) failed to recover to > or = 100/microl by day +18 post-transplant. The median number of days to recovery of ANC to 100/microl, 500/microl and 1000/microl, and of platelet counts to 20000/microl, 50000/microl and 100000/microl after either cycle 1 or cycle 2 of HDCT and the number of febrile days and platelet and PRBC transfusion requirements was not significantly different between the two arms of the study. The duration of hospitalization was similar between study arms for cycle 1 of HDCT, but was 3.5 days less with arm II compared to arm I (P = 0.0248) for cycle 2 of HDCT. The bone marrow buffy coat and PBSC product mononuclear cell count (x 10(8)/kg) and CD34+ cell count (x 10(6)/kg) collected by each method of stem cell mobilization was not significantly different. There is questionable clinical benefit with PBSC products mobilized with the combination of G-CSF and GM-CSF vs G-CSF alone. Perhaps different dosages, schedules, or other growth factor combinations with G-CSF might enhance these differences.

Adult↗

Transfusions of granulocyte-colony-stimulating factor-mobilized granulocyte components to allogeneic transplant recipients: analysis of kinetics and factors determining posttransfusion neutrophil and platelet counts.

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is a safe and effective agent for mobilization of neutrophils in normal donors, consistently resulting in cell yields per leukapheresis (LA) procedure that are superior to those with other agents. LA components also contain platelets, whose clinical relevance is unknown. STUDY DESIGN AND METHODS: This study describes the kinetics of and analyzes the factors determining the ANC and platelet count increments seen with each of three transfusions of granulocytes collected from HLA-matched sibling donors receiving G-CSF (n = 10; maximum of 3 LA procedures/donor). The transfusions were given to recipients (n = 10) on alternate days beginning. Day 1 after allogeneic bone marrow transplant (BMT). RESULTS: Significant, sustained increments in the recipient ANCs were observed after the transfusion of G-CSF-mobilized LA components. The mean peak posttransfusion increments in the ANCs were 1195, 729, and 631 per microL with transfusion of donor LA components on Days 1, 3, and 5, respectively. The length of time that the mean posttransfusion ANC was at or above the baseline (pretransfusion) value was 25 to 37 hours, depending on the post-BMT day when the component was administered. No consistent relationship was observed between LA component granulocyte dose, baseline recipient ANC, or temperature elevation and post-transfusion ANC increments. Large numbers of platelets (mean, 2.55 x 10(11)) were present in LA components, and this resulted in significant increments from baseline in the mean platelet count 1 hour after LA component transfusions. Between Days 1 and 7, the duration of severe neutropenia was shorter and the percentage of patients requiring nondonor platelet transfusions was less in study patients who received LA component transfusions than in a similar historical control group who did not. CONCLUSION: The transfusion of G-CSF-mobilized, HLA-matched LA components to allogeneic BMT recipients resulted in significant and sustained increments in the ANC and the platelet count. Within the range examined, a relationship between neutrophil dose and an increment in the ANC was not demonstrated.

Bone Marrow Transplantation↗

Factors that influence the collection and engraftment of allogeneic peripheral-blood stem cells in patients with hematologic malignancies.

PURPOSE: To determine the number of CD34+ cells associated with a high probability of rapid engraftment after allogeneic peripheral-blood stem-cell (PBSC) transplant, and to examine the relationship between certain donor characteristics and the effectiveness of PBSC mobilization. PATIENTS AND METHODS: Between December 1994 and July 1996, we treated 47 patients who had resistant hematologic neoplasms with myeloablative therapy followed by transplantation of allogeneic PBSC collected from histocompatible siblings after mobilization with granulocyte colony-stimulating factor (G-CSF). Expression of CD34 was determined by flow cytometry. RESULTS: Engraftment was rapid and similar to that observed following autologous PBSC transplant, with an absolute neutrophil count (ANC) greater than 500/microL and platelet count greater than 20,000/microL on median days +9 and +11, respectively. The pace of hematologic recovery correlated with the number of hematopoietic progenitors transplanted, so that patients who received greater than 5 x 10(6) CD34+ cells/kg recipient weight had a 95% likelihood of neutrophil and platelet recovery by day +15. Baseline (precytokine) CD34+ cells per milliliter of donor peripheral blood and total G-CSF dose (donor weight x 10 micrograms/kg) correlated with the number of CD34+ cells collected (R2 = .24 and P = .0009, and R2 = .24 and P < .0001, respectively). Donor age and sex did not effect mobilization. CONCLUSION: Following allogeneic PBSC transplant, patients who received greater than 5 x 10(6) CD34+ cells/ kg recipient weight had a high probability of rapid engraftment. Donors with low baseline levels of circulating progenitors (< 2,000 CD34+ cells/mL blood) and those who received lower total doses of G-CSF were less likely to be effectively mobilized. For donors with low baseline CD34+ counts, higher doses of G-CSF might improve mobilization. Baseline CD34+ counts and total G-CSF dose accounted for less than half of the variation in CD34+ cells collected, which indicates that other, as yet unidentified, factors play an important role in determining the effectiveness of mobilization.

Adolescent↗

A phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer.

To assess the feasibility of administering sequential cycles of dose-intensive therapy, 14 patients without prior chemotherapy for metastatic breast cancer were registered to be treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at an initial dose of 250 mg/m2 over 24 hours (day 1), followed by carboplatin dosed to an area under the concentration-time curve of 16 (calculated according to the Calvert formula), every 3 weeks for four cycles. This combination was supported with peripheral blood stem cells collected following granulocyte colony-stimulating factor with or without cyclophosphamide and paclitaxel. One patient failed to peripheralize CD34 cells after cyclophosphamide/paclitaxel therapy and was taken off protocol. The remaining 13 patients entered the paclitaxel/carboplatin phase of the program, and nine completed all four cycles. The median duration of severe neutropenia (absolute neutrophil count < 100/microL) was 6 days, despite the absence of routine use of granulocyte colony-stimulating factor. Only five of a total of 42 chemotherapy cycles (12%) were associated with febrile neutropenia requiring hospitalization. Most patients did not require platelet transfusions. The most significant nonhematologic toxicity was gastrointestinal (grade 3 in three patients, two of whom had received local radiation for relapse before chemotherapy). Most patients developed grade 1 or 2 sensory neuropathy by the final cycle. Of the nine patients who entered the paclitaxel/carboplatin phase and were evaluable for response, five achieved a complete remission. This doublet of high-dose therapy can be given in an entirely ambulatory setting and is associated with modest hematologic toxicity. The value of this option in the treatment of metastatic breast cancer compared with more conventional approaches to high-dose therapy will require a greater number of patients evaluable for response and longer follow-up.

Adult↗

Irreversible, severe congestive cardiomyopathy occurring in association with interferon alpha therapy.

Interferon alpha is a biologic agent with demonstrated anti-tumor activity in a variety of hematologic and solid malignancies. Many patients treated with interferon experience acute toxicity manifested as a flu-like syndrome of fever, chills, myalgias, and malaise. However, fatigue, anorexia, bone marrow suppression, nausea, vomiting, dizziness, and confusion may also occur. Cardiotoxicity is a rare complication of interferon therapy that most frequently presents as transient episodes of hypotension and tachycardia, with few significant life-threatening cardiovascular effects reported. A small number of cases of suspected interferon-induced cardiomyopathy, all of which improved after discontinuing interferon, have recently been documented. We report a patient with multiple myeloma who developed severe congestive cardiomyopathy while receiving interferon alpha that did not reverse subsequent to discontinuation of interferon therapy. Although the patient had previously received doxorubicin, the presence on endomyocardial biopsy of a prominent intracellular lipid accumulation within myocytes and only grade 2 anthracycline cardiotoxicity suggested that other or additional factor(s) contributed to the severity of this patient's cardiomyopathy. Etiologies of cardiac dysfunction other than interferon and doxorubicin were excluded. While a direct cause-effect relationship between interferon alpha and irreversible congestive cardiomyopathy cannot be firmly established in this case report, patients who either concurrently or sequentially receive interferon and anthracyclines should be carefully monitored for evidence of cardiac toxicity.

Combined Modality Therapy↗