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Biomedical subjects

S Bilgrami

Publications and source records attributed to S Bilgrami.

At least 19 recordsLinked to original sources

Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation.

BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis. PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation. The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis. RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion. Each of these patients was neutropenic and presented with fever. Three isolates demonstrated intermediate resistance to macrolides in vitro. However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy. CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia. Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses.

Adolescent↗

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.

Adult↗

Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 321 consecutive recipients of high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of vancomycin-resistant enterococcal (VRE) bacteremia. Ten patients developed VRE bacteremia at a median of 6 days following PBSCT. Nine isolates were Enterococcus faecium and one was E. faecalis. The median duration of bacteremia was 5 days. The central venous catheter was removed in seven individuals. Nine patients were treated with a variety of antimicrobial agents including quinupristin-dalfopristin, chloramphenicol, doxycycline, oral bacitracin, co-trimoxazole, and nitrofurantoin. Bacteremia resolved without adverse sequelae in seven patients. Two individuals who died of other causes had persistent or relapsed bacteremia at the time of death. An additional patient suffered multiple relapses of VRE bacteremia and died as a result of VRE endocarditis 605 days following PBSCT. Mortality as a direct result of VRE bacteremia was 10% in this series. The optimal type and duration of treatment of VRE bacteremia has not been clearly defined. Therefore, we perform weekly stool surveillance cultures for VRE in our hospitalized transplant population and apply strict barrier precautions in those individuals in whom stool colonization has been identified. Furthermore, the empiric use of vancomycin has been restricted. Bone Marrow Transplantation (2000) 25, 147-152.

Adolescent↗

Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer.

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.

Antineoplastic Agents, Hormonal↗

Kaposi's sarcoma following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia.

Unlike solid organ transplantation, Kaposi's sarcoma (KS) occurs rarely following hematopoietic stem cell transplantation (HSCT). In fact, only 5 cases of KS have been reported after allogeneic or autologous HSCT. The usual treatment combines a substantial decrease in, or elimination of, immunosuppressive therapy along with local measures such as surgical excision, cryotherapy or radiation therapy. A 46-year-old woman with chronic myelogenous leukemia who had received an allogeneic HSCT previously from an HLA-identical sibling, presented on day +814 with human herpes virus-8-associated KS involving her left lower extremity. She had been on continuous immunosuppressive therapy since her transplant because of chronic graft-versus-host disease. The intensity of immunosuppressive therapy was decreased once a diagnosis of KS had been established. However, the nodular lesions continued to progress in size and number. Therefore, a course of irradiation was administered to sites of bulk disease on her legs. Furthermore, thalidomide was initiated along with a topical retinoid, alitretinoin 0.1% gel applied twice daily to the nonirradiated lesions. This approach yielded a partial response in both irradiated and nonirradiated lesions over the course of the following 7 months. Both thalidomide and alitretinoin 0.1% gel appear to be beneficial in HSCT-associated KS and exhibit tolerable side effects.

Administration, Oral↗

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue.

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.

Adult↗

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.

Adolescent↗

Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence, risk factors, clinical features, complications, and outcome of cytomegalovirus (CMV) infection. A total of 26 patients (13%) developed CMV viremia (n = 5), DNAemia (n = 3), viruria (n = 18) and/or disease (n = 3) at a median of 45 days following stem cell infusion. None of the patients underwent surveillance testing for CMV. A diagnosis was established by culture and polymerase chain reaction of blood, urine or other tissue samples submitted when patients exhibited clinical features suggestive of CMV infection. Cytomegalovirus seropositivity prior to transplantation was the only statistically significant risk factor predicting subsequent identification of CMV (P < 0.001). The symptoms were severe enough in 23 patients to warrant treatment with intravenous ganciclovir. Three patients developed CMV disease; two developed fatal CMV pneumonia and one developed CMV gastritis which responded to antiviral treatment. Clinical signs and symptoms as well as viremia and viruria resolved with (20 patients) and without (three patients) treatment in the remaining individuals. All instances of CMV viremia, DNAemia, viruria and disease occurred within 3 months of stem cell infusion. These results demonstrate that CMV is a common pathogen after autologous PBSCT and may result in fatality in rare instances. Surveillance programs appear to be neither useful nor cost-effective. Diagnostic evaluation should be performed only in patients exhibiting suspicious clinical features and antiviral chemotherapy should be administered for persistent and severe signs and symptoms.

Adolescent↗

Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation for metastatic breast cancer: immunologic consequences affecting clinical outcome.

Autologous peripheral blood stem cell transplantation following myeloablative chemotherapy is being increasingly utilized in the treatment of a variety of malignancies. We administered busulfan 16 mg/kg orally, thiotepa 500-700 mg/m2 i.v., and carboplatin 800-1000 mg/m2 i.v. to 56 women with metastatic carcinoma of the breast. Autologous peripheral blood stem cells, which had been collected after a combination of chemotherapy and granulocyte colony-stimulating factor, were infused on day 0. The major toxicities of the conditioning regimen included severe pancytopenia, stomatitis, nausea, emesis, diarrhea, fever, and infection. Transplant-related mortality was 1.8%. The incidence of opportunistic viral infections was 42.9%. Fourteen individuals achieved a complete response. The actuarial survival at 1223 days was 13.7% for the entire group of patients; the actuarial survival at 1009 days was 39.3% among complete responders. The functional status of the immune system was determined following transplantation in a subset of patients. Peripheral blood mononuclear cells were obtained before and after stem cell infusion, and were analyzed phenotypically and functionally. Proliferative and interleukin-2 synthetic ability of these cells was assessed following stimulation with phytohemagglutinin and anti-CD3 antibody. The response to influenza peptides was also ascertained. Proliferative and interleukin-2 synthetic capacity was markedly impaired for over a year. Memory response was virtually absent for up to 2 years following transplantation. The prolonged and marked immunosuppression following this myeloablative regimen was associated with a high incidence of opportunistic viral infections, and may have contributed to disease relapse and progression especially in patients who failed to achieve a complete response following transplantation.

Administration, Oral↗

Regional thrombolysis with urokinase for central venous catheter-related thrombosis in patients undergoing high-dose chemotherapy with autologous blood stem cell rescue.

Fifty-one of 300 patients undergoing high-dose chemotherapy with (n = 245) or without (n = 55) autologous stem cell rescue developed central venous catheter-related thrombosis diagnosed by Doppler sonography or contrast venography. Eighteen of these individuals underwent regional thrombolysis defined as the infusion of urokinase into a superficial vein of the ipsilateral upper extremity in a dose not sufficient to produce systemic fibrinolysis by laboratory criteria. Urokinase was administered at a dose of 75,000-150,000 U/hour for 24 to 96 hours and contrast venography was performed to assess response. All individuals had a partial or complete resolution of clinical signs and symptoms. Fifty percent of patients also achieved a partial radiographic response defined as clot lysis with irregular canalization of the vein. Therapeutic doses of heparin for 5 to 7 days and warfarin for at least 3 months were commenced at the conclusion of urokinase therapy. Twelve catheters were salvaged and utilized subsequently until no longer required. Six catheters were removed because of poor catheter function or rethrombosis. The median interval from diagnosis of the thrombus until extraction of the 12 salvaged catheters was 3 months (range 1-8 months). Only a single patient who developed gastrointestinal bleeding required discontinuation of urokinase. Regional thrombolysis is safe, easy to administer, effective in many instances, less costly than the doses of antifibrinolytic agents required to induce systemic fibrinolysis, and should be considered in patients receiving high-dose chemotherapy with autologous stem cell rescue who develop central venous catheter-related thrombosis.

Adolescent↗

Streptococcus viridans bacteremia following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation was conducted to ascertain the incidence and outcome of Streptococcus viridans bacteremia as well as to determine the role of prophylactic ampicillin therapy in the peri-transplant setting. Viridans streptococci were isolated from the blood of 35 individuals at a median of 6 days (range 2-8 days) following stem cell infusion. The most common isolates were S. sanguis and S. mitis. All patients received ciprofloxacin orally during the peri-transplant period. Additionally, 79 patients received oral ampicillin prophylactically against gram-positive cocci. Although none of the patients suffered a fatal outcome, three individuals developed respiratory compromise requiring mechanical ventilation. Female sex proved to be the only independent risk factor for viridans streptococcal bacteremia (P=0.04). The shorter duration of neutropenia observed after stem cell transplantation did not impact on the incidence of S. viridans infections. Moreover, the prophylactic use of ampicillin failed to decrease the incidence of viridans sepsis and selected out organisms that were resistant to beta-lactam antibiotics.

Adolescent↗

Acanthamoeba meningoencephalitis following autologous peripheral stem cell transplantation.

Amoebic meningoencephalitis is an unusual complication of bone marrow transplantation. We report a case of Acanthamoeba meningoencephalitis in a patient with non-Hodgkin's lymphoma after autologous stem cell transplantation. Leg weakness, fever and urinary retention developed 69 days following transplantation. The patient then developed fever, generalized tonic clonic seizure, rapid deterioration of mental functions and hypercapneic respiratory failure. Magnetic resonance imaging demonstrated a ring enhancing lesion at the level of the thoracic spines 11 and 12. Examination of the cerebrospinal fluid revealed pleocytosis. Despite empiric therapy with broad-spectrum antimicrobial agents, the patient's condition worsened and she died 11 days following admission. Autopsy findings revealed a subacute meningoencephalitis secondary to Acanthamoeba culbertsoni.

Acanthamoeba↗

Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma following autologous stem cell transplantation.

Bacterial meningitis is an unusual complication of bone marrow transplantation. We report a case of Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma shortly after an autologous peripheral blood stem cell transplant. The infection resolved with a combination of intravenous penicillin G and chloramphenicol, and intrathecal vancomycin.

Bone Marrow Transplantation↗

Autologous peripheral blood progenitor cell transplantation for non-Hodgkin's lymphoma with extensive bone marrow necrosis.

A patient with malignant lymphoma, large cell type and extensive bone marrow necrosis at presentation is reported. Bone marrow necrosis persisted even after a complete remission was induced with standard chemotherapy. Because of this adverse prognostic factor, circulating stem cells were collected and reinfused following a myeloablative regimen consisting of busulfan, etoposide and cyclophosphamide. The patient engrafted rapidly and a subsequent bone marrow examination was free of both lymphoma and necrosis. To the best of our knowledge, this is the first reported patient with extensive bone marrow necrosis in whom circulating progenitor cells were harvested and utilized successfully.

Adult↗