Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: species identification and review of the literature.
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Trichoderma longibrachiatum was recovered from stool surveillance cultures and a perirectal ulcer biopsy specimen from a 29-year-old male who had received an allogeneic bone marrow transplant for acute lymphoblastic leukemia. The amphotericin B (2.0 microgram/ml) and itraconazole (1.0 microgram/ml) MICs for the organism were elevated. Therapy with these agents was unsuccessful, and the patient died on day 58 posttransplantation. At autopsy, histologic sections from the lungs, liver, brain, and intestinal wall showed infiltration by branching septate hyphae. Cultures were positive for Trichoderma longibrachiatum. While Trichoderma species have been recognized to be pathogenic in profoundly immunosuppressed hosts with increasing frequency, this is the first report of probable acquisition through the gastrointestinal tract. Salient features regarding the identification of molds in the Trichoderma longibrachiatum species aggregate are presented. (+info)
Effective treatment of autoimmune disease and progressive renal disease by mixed bone-marrow transplantation that establishes a stable mixed chimerism in BXSB recipient mice.
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Male BXSB mice spontaneously develop autoimmune disease with features similar to systemic lupus erythematosus. To determine whether this autoimmune disease can be treated as well as prevented by bone-marrow transplantation (BMT) and, at the same time, whether the immunity functions of lethally irradiated recipients can be reconstituted fully, male BXSB mice were engrafted with mixed T cell-depleted marrow (TCDM) both from fully allogeneic autoimmune-resistant BALB/c mice and from syngeneic autoimmune-prone BXSB mice, after the onset of autoimmune disease in the recipient mice. BMT with mixed TCDM from both resistant and susceptible strains of mice (mixed BMT) established stable mixed chimerism, prolonged the median life span, and arrested development of glomerulonephritis in BXSB mice. BMT with mixed TCDM also reduced the formation of anti-DNA antibodies that are observed typically in male mice of this strain. Furthermore, mixed BMT reconstituted the primary antibody production in BXSB recipients impressively. These findings indicate that transplantation of allogeneic autoimmune-resistant TCDM plus syngeneic autoimmune-prone TCDM into lethally irradiated BXSB mice can be used to treat autoimmune and renal disease in this strain of mice. In addition, this dual bone-marrow transplantation reconstitutes the immunity functions and avoids the immunodeficiencies that occur regularly in fully allogeneic chimeras after total body irradiation. This report describes an effective treatment of progressive renal disease and autoimmunity by establishing a stable mixed chimerism of TCDM transplantation from allogeneic autoimmune-resistant BALB/c mice plus syngeneic autoimmune-prone BXSB mice into BXSB mice. (+info)
Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group.
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PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies. (+info)
Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.
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PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy. (+info)
Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.
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PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis. (+info)
Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation.
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The recently described species Candida dubliniensis has been recovered primarily from superficial oral candidiasis in HIV-infected patients. No clinically documented invasive infections were reported until now in this patient group or in other immunocompromised patients. We report three cases of candidemia due to this newly emerging Candida species in HIV-negative patients with chemotherapy-induced immunosuppression and bone marrow transplantation. (+info)
High-dose therapy with autologous or allogeneic transplantation as salvage therapy for small cleaved cell lymphoma of follicular center cell origin.
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Between 1985 and 1996, 51 patients with relapsed or refractory small cleaved cell lymphoma (SCCL) received high-dose chemotherapy +/- TBI in conjunction with autologous (ABMT) (36 patients) or allogeneic transplantation (15 patients). Patients were eligible for ABMT if the bone marrow biopsy done prior to the planned transplant did not reveal microscopic involvement with SCCL. Patients receiving ABMT had a median age of 48 years, had received a median of 2.5 chemotherapy regimens prior to transplantation, and were transplanted a median of 35.5 months from diagnosis. Among patients receiving ABMT, 5 year actuarial survival was 56+/-11%. Median survival was 126+ months, and median survival from diagnosis was 191 months. Univariate and multivariate analysis identified sensitive disease as the best predictor of a favorable response. Five-year actuarial survival was 66+/-12% for patients with sensitive disease at the time of transplant as compared to 29+/-17% for patients with resistant disease, P = 0.015. Median survival in patients with sensitive disease at the time of ABMT was 126+ months. By univariate analysis, survival was significantly better for patients receiving ABMT as compared to patients receiving allogeneic transplants. Median survival following allogeneic transplantation was 5 months; 5 year actuarial survival was 15+/-13%. In a multivariate analysis, which considered autologous vs allogeneic transplantation, sensitive vs resistant disease, <3 vs > or = 3 prior treatments, and prior bone marrow involvement, allogeneic transplantation was significantly associated with poor survival. Treatment-related mortality occurred in eight of 15 patients receiving allogeneic transplantation and limited the effectiveness of this therapy. High-dose therapy in conjunction with ABMT is effective therapy for patients with SCCL whose disease is sensitive to chemotherapy and whose marrows are microscopically free of disease. Because of possible selection bias, it has not been proven that this approach increases survival in these patients. Treatment-related mortality limits the effectiveness of allogeneic transplantation in SCCL. (+info)
Single leukapheresis products collected from healthy donors after the administration of granulocyte colony-stimulating factor contain ten-fold higher numbers of long-term reconstituting hematopoietic progenitor cells than conventional bone marrow allografts.
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Cytokine-mobilized peripheral blood progenitor cells (PBPCs) have been used successfully for hematopoietic reconstitution following allogeneic transplantation. The ease of harvest, the faster engraftment and the high yield of CD34+ cells have made this source of hematopoietic progenitor cells (HPCs) an attractive alternative to bone marrow (BM). In the present study we compared the engraftment potential of conventional BM allografts and single leukapheresis products (LPs) collected from healthy donors following the administration of granulocyte colony-stimulating factor (G-CSF). For this, lineage-committed and primitive HPCs were assessed by flow cytometry and by colony- and cobblestone area-forming cell (CFC, CAFC) assays. Mean numbers of CD34+ cells in LPs (n = 11) were similar to that of BM grafts (n = 12) (278+/-57 vs 227+/-34 x 10(6) CD34+ cells). The frequencies of CFCs, week 5 CAFCs and week 8 CAFCs were 1.6-, 8.4- and 10.3-fold higher in the CD34+ compartment of mobilized blood than that of marrow, resulting in significantly higher yields of clonogenic HPCs in LPs when compared to BM grafts. We conclude that G-CSF preferentially mobilizes clonogenic progenitors capable of short- and, in particular, longterm reconstitution, and that the engraftment potential of single LPs is superior to that of BM allografts. Hence, the use of PBPCs may be favorable for protocols that include graft manipulations with expected cell loss (eg T cell depletion, CD34+ selection). PBPCs may also be advantageous for gene therapy trials due to their high numbers of potential target cells (eg CAFCs). (+info)