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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P =.01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell-depleted allogeneic stem cell transplantation.
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PMID:Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. 1073 91

The optimal approach for stem cell transplantation in children with immunodeficiency has yet to be determined. Conditioning therapy is necessary for reliable engraftment and full immune reconstitution; however, the beneficial effect of cytoreductive conditioning is counterbalanced by increased short- and long-term treatment-related toxicity. Whether bone marrow transplantation with a nonmyeloablative preparative regimen was sufficient for the establishment of donor immune reconstitution, with the resultant correction of disease phenotype, was investigated. Eight patients with severe immunodeficiency states underwent T-cell replete bone marrow transplantation from a human leukocyte antigen-matched unrelated (n = 6) or sibling (n = 2) donor with nonmyeloablative conditioning using a fludarabine-melphalan-anti-lymphocyte globulin-based regimen. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. All patients were engrafted with predominantly donor hematopoiesis, and the duration of neutropenia was brief. Significant acute graft-versus-host disease (GVHD) did not develop, but one patient had limited chronic GVHD. One patient died of disease recurrence, and 3 have stable, mixed chimerism. At a median follow-up of 1 year, all patients have had good recovery of CD3(+) T-cell numbers, and 6 of 7 evaluable patients have normal phytohemagglutinin stimulation indices. The rate of immune reconstitution is comparable with that of historical controls undergoing standard myeloablative protocols. Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. In summary, it has been demonstrated that nonmyeloablative stem cell transplantation permits rapid engraftment from both sibling and unrelated donors with minimal toxicity even in the presence of severe organ dysfunction. If long-term immune reconstitution of patients treated with this protocol is demonstrated, it is believed this approach might offer significant advantages compared with standard protocols by combining adequate immune reconstitution with reduced short- and long-term toxicity. (Blood. 2000;96:1239-1246)
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PMID:Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. 1094 63

Hematopoietic colony-stimulating factors (CSF) decrease the duration of neutropenia following stem cell transplantation (SCT). With CSF-mobilized allogeneic blood SCT (alloBSCT), the yields of CD34+ cells are several-fold higher than in other SCT settings, raising concern that post-transplant CSF use may be unnecessary. In this study, we estimate the resource and cost implications associated with CSF use following alloBSCT. A cost identification analysis was conducted for 44 patients on a randomized, double-blind placebo-controlled trial of G-CSF following alloBSCT. Study drug was given daily until an absolute neutrophil count (ANC) > or = 1000 cells/microl. Billing information from the time of transplant to day +100 was analyzed. The median number of days to an ANC > or = 500 cells/microl was shorter in the G-CSF arm, 10.5 days vs 15 days (P < 0.001), while platelet recovery and rates of acute graft-versus-host disease (GVHD) and survival were similar. Resource use was similar, including days hospitalized, days on antibiotics, blood products transfused and outpatient visits. Total median post-transplant costs were $76577 for G-CSF patients and $78799 for placebo patients (P = 0.93). G-CSF following allogeneic blood SCT decreased the median duration of absolute neutropenia and did not incur additional costs, but did not result in shorter hospitalizations, or less frequent antibiotic use.
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PMID:Economic analysis of a phase III study of G-CSF vs placebo following allogeneic blood stem cell transplantation. 1104 69

In a randomized, placebo-controlled, double-blind trial, thalidomide or placebo together with glucocorticoids and either cyclosporine or tacrolimus was administered as initial therapy for clinical extensive chronic graft-versus-host disease (cGVHD). All patients had thrombocytopenia or cGVHD that evolved directly from acute GVHD as an indicator of a poor prognosis. The study drug (thalidomide or placebo) was administered initially at a dose of 200 mg orally per day, followed by a gradual increase to 800 mg/d if side effects were tolerable. Treatment with the study drug was discontinued before resolution of cGVHD in 23 (92%) of the 25 patients who received thalidomide and in 17 (65%) of the 26 patients who received placebo (P =.02). Neutropenia and neurologic symptoms were the most frequent reasons for early discontinuation of treatment with thalidomide. The duration of treatment with thalidomide was too short to assess its efficacy in controlling cGVHD. (Blood. 2000;96:3995-3996)
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PMID:Thalidomide for treatment of patients with chronic graft-versus-host disease. 1109 92

After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital.
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PMID:Is it safe to treat allogeneic stem cell transplant recipients at home during the pancytopenic phase? A pilot trial. 1110 3

The efficacy and side effects of intermediate-dose cytarabine, idarubicin plus etoposide and subsequent donor leukocyte infusion (DLI) were investigated in patients with acute leukemia who relapsed after allogeneic bone marrow transplantation (BMT). Patients were given cytarabine continuous i.v. (1 g/m2 per day x 5), idarubicin i.v. (12 mg/m2 per day x 3), and etoposide i.v. infusion (150 mg/m2 per day x 3). Two days later, G-CSF mobilized donor leukocytes were infused for 2 days. No graft-versus-host disease (GVHD) prophylaxis was given. Between August 1997 and February 2000, 13 patients enrolled (eight acute myeloid leukemia (AML) and five acute lymphoblastic leukemia (ALL)). All patients finished chemotherapy and DLI. Eleven patients (85%) achieved complete remission (CR) at median 27 days after DLI. After median follow up of 10.9 months (2.5-33.3), five of 11 patients who achieved CR relapsed. Overall, six of 13 patients were surviving (6/8 AML and 0/5 ALL, P=0.059). Marrow recovery after chemotherapy and DLI was rapid (12 days for absolute neutrophil count (ANC) >500/microl). Side effects included fever with neutropenia (100%), pneumonia (46%), grade II-IV mucositis (69%), grade III-IV acute GVHD (45%), and extensive chronic GVHD (64%). One patient died from chronic GVHD. Chemotherapy containing intermediate-dose cytarabine and DLI produced a high CR rate in acute leukemia in relapse after allogeneic BMT. A fraction of patients are surviving long term. Side effects were substantial but manageable.
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PMID:Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. 1124 27

After primary recovery of platelet counts after transplantation, there can be a late persistent decline called secondary failure of platelet recovery (SFPR), which may occur although the counts of other cell lineages remain within the normal range. SFPR was defined as a decline of platelet counts below 20,000/microL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts > or = 50,000/microL without transfusions for 7 consecutive days after hematopoietic stem cell transplantation (HSCT). The study population consisted of 2871 consecutive patients receiving transplants from January 1990 to March 1997. After primary recovery of platelet counts, SFPR not due to relapse of the underlying disease was observed in 285 of 1401 (20%) patients undergoing allogeneic transplantation and 36 (8%) of 444 patients undergoing autologous transplantation, with a median time of onset after transplantation at day 63 (range, day 21-156) and day 44 (range, day 24-89), respectively. Concomitant neutropenia was seen in 57 (20%) of 285 patients undergoing allogeneic HSCT and 7 (19%) of 36 patients undergoing autologous HSCT with SFPR. By multivariable analysis, the following were factors significantly associated with SFPR after allogeneic HSCT: a transplant from an unrelated donor; a graft-versus-host disease (GVHD) prophylaxis other than methotrexate and cyclosporine; development of grade 2 through 4 acute GVHD; impaired renal or liver function; conditioning with the combination of busulfan, cyclophosphamide, and total body irradiation; stem cell dose; and infections. Cytomegalovirus infection after engraftment and source of stem cells were the only significant risk factors after autologous HSCT. The hazard rate of death was significantly higher in patients who experienced SFPR (hazard ratio = 2.6 for allogeneic HSCT; hazard ratio = 2.2 for autologous HSCT). SFPR was associated with serious complications and poor outcome after transplantation. The identification of the characteristics and risk factors for SFPR could improve patient counseling and management and lead to the design of effective treatment strategies.
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PMID:Secondary failure of platelet recovery after hematopoietic stem cell transplantation. 1130 49

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.
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PMID:Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan. 1131 74

In the standard treatment of patients with haematological malignancy, immunosuppressive therapy produces prolonged periods of neutropenia and mucositis, which increase the risk of systemic fungal infection. In allogeneic bone marrow transplantation, this risk extends well beyond the period of neutropenia when graft-versus-host disease, and its treatment, result in prolonged lymphocytopenia. Various agents are used for antifungal prophylaxis and treatment but all have limitations: amphotericin B is restricted by the need for intravenous infusion and the occurrence of adverse events, fluconazole by its narrow spectrum of activity and the emergence of fluconazole-resistant fungi and itraconazole capsules by erratic absorption. Oral administration of antifungals has clear advantages in prophylaxis and an important current strategy is to maximize the extent and reliability of the oral bioavailability of antifungal agents. Mucositis is the main obstacle for success of strategies based on oral delivery. In this review, the ability of these new oral formulations to deliver sufficient antifungal prophylaxis is evaluated.
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PMID:Oral antifungals as prophylaxis in haematological malignancy. 1133 34

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.
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PMID:Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation. 1159 23


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