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B J Bolwell

Publications and source records attributed to B J Bolwell.

At least 19 recordsLinked to original sources

Allogeneic BMT and patient eligibility based on psychosocial criteria: a survey of BMT professionals.

BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.

Bone Marrow Transplantation↗

High-dose busulfan, cyclophosphamide, and etoposide does not improve outcome of allogeneic stem cell transplantation compared to BuCy2 in patients with acute myeloid leukemia.

SUMMARY: To reduce relapse following allogeneic transplantation for AML, intensification of high-dose busulfan/cyclophosphamide using additional agents has been investigated but with few reported comparisons. We compared an intensified regimen of etoposide (60 mg/kg), busulphan (14 mg/kg), and cyclophosphamide (120 mg/kg) (BuCyVP) with BuCy2 in 237 AML patients. No significant difference in overall outcome was observed following BuCyVP (n=127) or BuCy2 (n=110). The 5-year survival was 27.3 and 30.1% following BuCyVP and BuCy2, respectively (P=0.48). Similarly, the 5-year cumulative incidence of relapse (CIR) was 28.3 and 34.8% with BuCyVP and BuCy2 (P=0.45), respectively. On multivariable analysis, patients transplanted in CR1 (P=0.002) and from related donors (P=0.013) had longer survival, while disease status at transplant was the only factor predicting CIR (P=0.002). In a separate analysis of CR1 patients (n=56), there was no significant difference in survival (P=0.37) or CIR (P=0.87) between the two regimens. However, for more advanced disease, there was a trend towards less relapse with BuCyVP (P=0.08), which was balanced by a higher cumulative incidence of transplant-related deaths (P=0.03) compared to BuCy2, resulting in similar survival. Overall, our results do not support the use of the more intensive BuCyVP regimen over BuCy2 in either early or more advanced disease AML patients.

Acute Disease↗

Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival.

Allograft dendritic cell (DC) content has been identified as a predictor of relapse and event-free survival after allogeneic bone marrow transplantation. However, the prognostic importance of DCs has not been evaluated in the setting of autologous hematopoietic stem cell transplantation (HSCT). We prospectively determined pre-transplant and post transplant DC levels, including DC1 and DC2 subset levels, in 53 patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBC NHL) undergoing autologous HSCT. Pre-transplant DCs were measured in the collected stem cell products and were therefore indicative of cell numbers infused directly into patients; post transplant analysis of DCs was performed on the peripheral blood of patients 6 weeks after the infusion of autologous stem cells. Higher pre-transplant levels of DC1 cells and total DCs were significantly associated with improved survival. Similarly, greater post transplant levels of total DCs and both subsets were significantly associated with survival. These findings suggest a relationship between DC reconstitution and survival following autologous HSCT for DLBC NHL. Strategies to increase autograft DC content or accelerate DC recovery after autologous HSCT might improve outcomes in this setting.

Adult↗

Clinical outcomes of patients with impaired left ventricular ejection fraction undergoing autologous bone marrow transplantation: can we safely transplant patients with impaired ejection fraction?

Experience with autologous bone marrow transplantation (ABMT) in patients with impaired left ventricular ejection fraction (LVEF) or heart failure (HF) is limited. We identified 308 consecutive patients who underwent ABMT for Hodgkin's or non-Hodgkin's lymphoma at our institution (1996-2003). Patient characteristics, clinical course and overall survival were compared between patients with preserved ( > or = 50%) or impaired ( < 50%) LVEF. Of the 308 patients identified, 20 had baseline impaired LVEF (four with LVEF < or = 40%, all NYHA class I-II HF). None of the patients with post-ABMT echocardiogram had worsened LVEF (n = 7). Among the 20 patients with impaired LVEF, four patients had reversible cardiac complications post-ABMT (including worsening HF). The two deaths observed in the impaired LVEF group were both due to noncardiac causes. The 5-year survival was similar between patients with preserved and impaired LVEF (P = 0.43). Careful selection of patients with stable, mild-to-moderate HF and impaired LVEF for ABMT can achieve similar long-term survival. As medical care for HF and ABMT improves, the exclusion criteria for ABMT with regard to HF and impaired LVEF should be re-examined.

Adult↗

Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.

Bone Marrow Transplantation↗

Syngeneic graft-versus-host disease: a report of two cases and literature review.

Rappeport et al first reported the clinical syndrome of graft-versus-host disease (GVHD) in syngeneic bone marrow transplant patients. Recently, there have been more reports of a GVHD-like syndrome in syngeneic bone marrow transplant patients (SGVHD) that may result in significant clinical morbidity. A total of 17 cases of SGVHD in syngeneic bone marrow transplant patients have been reported to date in the medical literature. The current report reviews these cases and presents two additional cases of severe SGVHD that have occurred at our institution.

Adult↗

Are predictive factors clinically useful in bone marrow transplantation?

Variables that accurately predict the clinical outcome of any procedure, including bone marrow transplantation (BMT), are of paramount importance when assessing the risks and benefits of the procedure. This review of the world's literature of variables affecting overall outcome after myeloablative BMT critically appraises the value of many bone marrow transplant dogmas. There is a relative paucity of data supporting many commonly used transplant practices, including having an upper age limit for eligibility criteria, and absolute requirements for cardiac and pulmonary function pre transplant. In contrast, recently published literature suggests that several parameters occurring soon after a BMT has been performed may accurately predict transplant outcome. Ultimately, given the rapidly evolving nature of BMT, renewed clinical research of variables predictive of transplant outcome is needed.

Bone Marrow Transplantation↗

The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.

Ambulatory Care↗

A multivariable analysis of factors influencing mucositis after autologous progenitor cell transplantation.

Mucositis is a common and vexing complication of autologous progenitor cell transplantation (ABMT). A modified oral mucositis assessment scale (OMAS) has been found to be a reproducible and effective tool for monitoring mucositis after radiation therapy or chemotherapy. We utilized the modified OMAS scale to study clinical parameters associated with the development of mucositis in 79 patients undergoing ABMT. Median patient age was 52; 61% had non-Hodgkin's lymphoma (NHL), 23% multiple myeloma and 14% Hodgkin's disease. Patients were mobilized with G-CSF alone or the combination of etoposide plus G-CSF. Univariable correlates of worse mucositis were prior radiation therapy (P = 0.004), a diagnosis of NHL (P = 0.014), progenitor cell mobilizing regimen containing etoposide (P = 0.001), and ABMT preparative regimen containing etoposide (P = 0.006). Multivariable regression analysis revealed that NHL diagnosis (P = 0.007), prior radiation therapy (P = 0.001), and etoposide in the mobilizing regimen (P = 0.034) were associated with worse post-transplant mucositis. Worsening mucositis correlated with a longer inpatient length of stay. We conclude that several variables contribute to worsening mucositis during autologous transplantation, including etoposide in the progenitor cell mobilizing regimen.

Etoposide↗

The effect of pretransplant interferon therapy on the outcome of unrelated donor hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in first chronic phase.

Various therapeutic options are available for patients with chronic myelogenous leukemia. Allogeneic stem cell transplantation, though often curative, is associated with high nonrelapse mortality and long-term morbidity, particularly when cells from unrelated donors are used. Many physicians and patients opt for a trial of interferon-alpha (IFN)-based therapy first, reserving transplantation for patients with inadequate response or intolerance to IFN. Data were analyzed on 740 patients receiving unrelated donor transplants for chronic myelogenous leukemia in first chronic phase provided by the International Bone Marrow Transplant Registry and the National Marrow Donor Program to see whether IFN pretreatment compromised transplantation outcome. A total of 489 (66%) had received IFN prior to transplantation; 251 (34%) had not. Disease characteristics in the 2 groups were similar at diagnosis but at the time of transplantation, hematologic parameters and weight were lower in IFN patients and the interval between diagnosis and transplantation was longer. After adjustment for baseline covariates, no effect of IFN exposure was found on overall survival, leukemia-free survival, nonrelapse mortality, engraftment, relapse, or acute or chronic graft-versus-host disease. Evaluation of effects based on duration of therapy and time off IFN prior to transplantation was limited by missing data and confounding with IFN intolerance and disease responsiveness. In conclusion, no evidence was found for an independent adverse effect of IFN pretreatment on the outcome of subsequent unrelated donor transplantation.

Acute Disease↗

Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL.

ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and initiates cell killing through complement-mediated lysis. In a dose-finding trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD) received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per day. All patients had undergone allogeneic transplantation for malignant or nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate- and cyclosporine-containing regimens. None responded to methylprednisolone, given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days after transplantation; it was given for 7 consecutive days and was followed by 2 infusions per week for 2 more weeks. Among 51 patients evaluable for efficacy, 26 (51%) responded, including 13 with complete responses (CR) and 13 with partial responses (PR). CR lasting 14 days or longer or PR lasting 7 days or longer occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%) patients who received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%) patients given 0.01 mg/kg per day. Myalgias at doses 0.2 mg/kg or greater were dose limiting and resolved without sequelae. Causes of death included organ failure, progressive GVHD, and infection. No death was attributed to ABX-CBL. At 6 months after the initiation of ABX-CBL therapy, 26 (44%) patients were surviving. These results are encouraging. Further studies on the use of ABX-CBL in the management of GVHD are warranted.

Acute Disease↗

Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.

Adolescent↗

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗

Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation.

Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.

Adult↗

Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma.

The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.

Antineoplastic Combined Chemotherapy Protocols↗

A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy.

Despite an extensive literature, no consensus has emerged regarding the optimal preventive strategy for CMV in allogeneic bone marrow transplantation (BMT). No survey of CMV prevention in BMT centers in the United States has yet been published. A questionnaire was sent to all allogeneic BMT programs in the United States, as listed in the November 1998 National Marrow Donor Program (NMDP) address roster. Questions included whether universal prophylaxis, pre-emptive therapy, or some other strategy was used for CMV prevention, and which CMV diagnostic tests were utilized. Eighty-one of 96 programs (86%) responded to the survey. Of these, 46 (56%) utilize a pre-emptive ganciclovir strategy, whereas 17 (21%) utilize universal prophylaxis, and 15 (19%) utilize a hybrid strategy based on risk stratification. The most commonly utilized CMV diagnostic tests are CMV-DNA by PCR (55 centers), shell vial centrifugation culture (52), tissue culture (42), pp65 antigenemia assay (38), and CMV-DNA by Digene hybrid capture (14). Of these, the CMV-DNA by PCR, pp65 antigenemia assay, and shell vial culture are the most frequently utilized as triggers for pre-emptive therapy. Quantitative assays are common (PCR 42%, Digene 64%). We conclude that centers currently performing allogeneic BMT in the United States employ a variety of strategies for CMV prevention, and differ in their diagnostic tests of choice for CMV monitoring. These results emphasize the need for large-scale studies to identify optimal diagnostic and management protocols. Bone Marrow Transplantation (2000) 26, 763-767.

Bone Marrow Transplantation↗

Protracted results of dose-intensive therapy using cyclophosphamide, carmustine, and continuous infusion etoposide with autologous stem cell support in patients with relapse or refractory Hodgkin's disease: a phase II study from the North American Marrow Transplant Group.

To determine the long-term results of high-dose chemotherapy and stem cell support in relapsed or primary refractory Hodgkin disease patients. One hundred and thirty-one patients with relapsed or primary refractory Hodgkin's disease were treated with a dose-intensive therapy protocol consisting of etoposide (2400 mg/m2 continuous intravenous infusion) cyclophosphamide (7200 mg/m2 intravenously), and carmustine (300-600 mg/m2 intravenously) CBVi. All patients had previously failed conventional chemoradiotherapy. Severe toxicities were related to infectious, hepatic, and pulmonary complications. Fatal, regimen-related toxicity was 19%; liver and lung dysfunction, as well as infection, were the most frequent problems. Ninety-one (69%) of the patients achieved a complete response (CR) (95% CI = 59% to 75%) after CBVi and autologous stem cell infusion. With a median follow-up of 5.1 years (range 3.0 to 9.5 years), overall and event-free survival are 44% (95% CI = 33% to 47%) and 38% (95% CI = 28% to 46%) respectively. While univariate analysis did not reveal a statistically significant variable to predict a better response, responsiveness to therapy demonstrated a trend. We conclude that CBVi is an effective therapy for relapsed or refractory Hodgkin's disease, producing long-term, durable remissions.

Adolescent↗

Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial.

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

Breast Neoplasms↗