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Issam I Raad - One of the best experts on this subject based on the ideXlab platform.
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granulocyte transfusions in Hematologic Malignancy patients with invasive pulmonary aspergillosis outcomes and complications
Annals of Oncology, 2013Co-Authors: Issam I Raad, Anne Marie Chaftari, M Al M Shuaibi, Ying Jiang, William Shomali, Jorge E Cortes, Benjamin Lichtiger, Ray Y HachemAbstract:Abstract Background Granulocyte transfusions (GTXs) have been used successfully as an adjunctive treatment option for invasive infections in some neutropenic patients with underlying Hematologic Malignancy (HM). Patients and methods We sought to determine the impact of GTX as an adjunct to antifungal therapy in 128 patients with HM and prolonged neutropenia (≥14 days) with a proven or probable invasive aspergillosis (IA) infection by retrospectively reviewing our institutional database. Results Fifty-three patients received GTX and 75 did not. By univariate analysis, patients with invasive pulmonary aspergillosis who received GTX were less likely to respond to antifungal therapy (P = 0.03), and more likely to die of IA (P = 0.009) when compared with the non-GTX group. Among patients who received GTX, 53% developed a pulmonary reaction. Furthermore, IA-related death was associated with the number of GTX given (P = 0.018) and the early initiation of GTX within 7 days after starting antifungal therapy (P = 0.001). By multivariate competing risk analysis, patients who received GTX were more likely to die of IA than patients who did not receive GTX (P = 0.011). Conclusions Our study suggests that GTX does not improve response to antifungal therapy and is associated with worse outcomes of IA infection in HM patients, particularly those with pulmonary involvement.
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utility of galactomannan enzyme immunoassay and 1 3 β d glucan in diagnosis of invasive fungal infections low sensitivity for aspergillus fumigatus infection in Hematologic Malignancy patients
Journal of Clinical Microbiology, 2009Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Roy F Chemaly, Yunfang Jiang, Ruth Reitzel, Issam I RaadAbstract:Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in Hematologic Malignancy patients.
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amphotericin b lipid complex versus liposomal amphotericin b monotherapy for invasive aspergillosis in patients with Hematologic Malignancy
Cancer, 2008Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Hend Hanna, Maha Boktour, Rola Husni, Harrys A Torres, Claude Afif, Issam I RaadAbstract:BACKGROUND. Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with Hematologic Malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS. The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n = 106) or ABLC (n = 52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the Hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS. Risk factors for IA, such as underlying Malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7–15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P < .001). CONCLUSIONS. Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting. Cancer 2008. © 2008 American Cancer Society.
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posaconazole as salvage treatment for invasive fusariosis in patients with underlying Hematologic Malignancy and other conditions
Clinical Infectious Diseases, 2006Co-Authors: Issam I Raad, Ray Y Hachem, Raoul Herbrecht, John R. Graybill, Roberta S. Hare, Gavin Corcoran, Dimitrios P. KontoyiannisAbstract:Background. Conventional amphotericin B–based antifungal therapy for invasive fusariosis in patients with a Hematologic Malignancy results in a 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. Methods. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. Results. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for 13 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. Conclusion. These results suggest that posaconazole is useful for the treatment of invasive fusariosis. After Aspergillus species, Fusarium species are among the leading fungal pathogens to cause invasive mold infection in patients with underlying Hematologic Malignancy and in those who have undergone hematopoietic stem cell transplantation (HSCT) [1–3]. Mortality rates associated with fusariosis have equaled or exceeded 70% [2, 4], and progression in high-risk patients is often fulminant, leaving a narrow window of opportunity for therapeutic intervention. The primary antifungal therapy is amphotericin B or its lipid formulations [2, 5, 6]; however, this therapy is of limited efficacy because of its potential toxicity and poor activity against Fusarium organisms in vivo. Other treatment options include voriconazole, which is indicated for the treatment of fusariosis in patients intolerant of or with disease refractory to other therapy.
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Posaconazole as Salvage Treatment for Invasive Fusariosis in Patients with Underlying Hematologic Malignancy and Other Conditions
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2006Co-Authors: Issam I Raad, Ray Y Hachem, Raoul Herbrecht, John R. Graybill, Roberta S. Hare, Gavin Corcoran, Dimitrios P. KontoyiannisAbstract:Conventional amphotericin B-based antifungal therapy for invasive fusariosis in patients with a Hematologic Malignancy results in a > or = 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for >3 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. These results suggest that posaconazole is useful for the treatment of invasive fusariosis.
Meijie Zhang - One of the best experts on this subject based on the ideXlab platform.
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optimal donor for african americans with Hematologic Malignancy hla haploidentical relative or umbilical cord blood transplant
Biology of Blood and Marrow Transplantation, 2020Co-Authors: Scott R Solomon, Lee Ann Baxterlowe, Claudio G. Brunstein, Meijie Zhang, Karen K Ballen, Andrew St Martin, Asad Bashey, Minoo Battiwalla, Saurabh ChhabraAbstract:ABSTRACT Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for Hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with Hematologic Malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P
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the effect of donor characteristics on survival after unrelated donor transplantation for Hematologic Malignancy
Blood, 2016Co-Authors: Craig Kollman, Stephen R Spellman, Claudio Anasetti, Meijie Zhang, Anna Hassebroek, Joseph H Antin, Richard E Champlin, Dennis L Confer, John F DipersioAbstract:There are >24 million registered adult donors, and the numbers of unrelated donor transplantations are increasing. The optimal strategy for prioritizing among comparably HLA-matched potential donors has not been established. Therefore, the objective of the current analyses was to study the association between donor characteristics (age, sex, parity, cytomegalovirus serostatus, HLA match, and blood group ABO match) and survival after transplantation for Hematologic Malignancy. The association of donor characteristics with transplantation outcomes was examined using either logistic or Cox regression models, adjusting for patient disease and transplantation characteristics associated with outcomes in 2 independent datasets: 1988 to 2006 (N = 6349; training cohort) and 2007 to 2011 (N = 4690; validation cohort). All donor-recipient pairs had allele-level HLA typing at HLA-A, -B, -C, and -DRB1, which is the current standard for selecting donors. Adjusting for patient disease and transplantation characteristics, survival was better after transplantation of grafts from young donors (aged 18-32 years) who were HLA matched to recipients (P < .001). These findings were validated for transplantations that occurred between 2007 and 2011. For every 10-year increment in donor age, there is a 5.5% increase in the hazard ratio for overall mortality. Increasing HLA disparity was also associated with worsening survival. Donor age and donor-recipient HLA match are important when selecting adult unrelated donors. Other donor characteristics such as sex, parity, and cytomegalovirus serostatus were not associated with survival. The effect of ABO matching on survival is modest and must be studied further before definitive recommendations can be offered.
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effect of hla matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for Hematologic Malignancy
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Vanderson Rocha, Annalisa Ruggeri, Stephen R Spellman, Lee Ann Baxterlowe, Meijie Zhang, Duncan Purtill, Colleen Brady, Etienne Baudoux, Paola Bergamaschi, Robert ChowAbstract:Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non–NIMA-matched UCBTs. All patients had a Hematologic Malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs ( P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.
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donor leukocyte infusions to treat Hematologic Malignancy relapse following allo sct in a pediatric population
Bone Marrow Transplantation, 2008Co-Authors: John E Levine, Meijie Zhang, A J Barrett, M Arora, Michael A Pulsipher, Nancy Bunin, J Fort, Fausto R Loberiza, David L Porter, Sergio GiraltAbstract:Donor leukocyte infusions (DLI) can reverse relapse of Hematologic Malignancy following allogeneic hematopoietic stem cell transplant (HSCT) in some cases. Little is known regarding the effectiveness of DLI in children who relapse after HSCT. We report outcomes of 49 children who received DLI for relapse after allogeneic transplant. Prognosis was particularly poor (0/14 responses) for patients relapsing within 6 months from transplant. DLI rarely induced remission when given as sole therapy for marrow relapse. One-year disease-free survival was 30% (6/20) in patients who received DLI as consolidation following chemotherapy. The development of GVHD grades 1-2 was associated with superior 3-year survival than patients who developed GVHD grades 3-4 (P<0.002). To determine the benefit of DLI, 45 children who received DLI for relapse (four children without matches were excluded) were compared to 1229 children with similar characteristics whose relapse was not treated with DLI. There was no difference in survival (P=0.30) once adjustments were made to account for the time from relapse to DLI. Although a few children achieved durable remissions when DLI was used as part of a post-relapse treatment strategy, DLI was unsuccessful in the majority of cases. Strategies may be better directed at preempting post transplant relapse.
Dimitrios P. Kontoyiannis - One of the best experts on this subject based on the ideXlab platform.
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lack of toxicity with long term isavuconazole use in patients with Hematologic Malignancy
Clinical Infectious Diseases, 2019Co-Authors: Adam J Dipippo, Dimitrios P. KontoyiannisAbstract:Prolonged courses of isavuconazole (ISA) are increasingly utilized in immunocompromised patients. Toxicities have been reported with long-term use of the other triazoles. We report the first real-life tolerability data in 50 patients with Hematologic Malignancy receiving ≥6 months of ISA. ISA was well tolerated in our ill patient population.
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utility of galactomannan enzyme immunoassay and 1 3 β d glucan in diagnosis of invasive fungal infections low sensitivity for aspergillus fumigatus infection in Hematologic Malignancy patients
Journal of Clinical Microbiology, 2009Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Roy F Chemaly, Yunfang Jiang, Ruth Reitzel, Issam I RaadAbstract:Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in Hematologic Malignancy patients.
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delaying amphotericin b based frontline therapy significantly increases mortality among patients with Hematologic Malignancy who have zygomycosis
Clinical Infectious Diseases, 2008Co-Authors: Georgios Chamilos, Russell E Lewis, Dimitrios P. KontoyiannisAbstract:Background Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. Methods We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with Hematologic Malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. Results Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active Malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome. Conclusions Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with Hematological Malignancy who are at an increased risk for zygomycosis.
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amphotericin b lipid complex versus liposomal amphotericin b monotherapy for invasive aspergillosis in patients with Hematologic Malignancy
Cancer, 2008Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Hend Hanna, Maha Boktour, Rola Husni, Harrys A Torres, Claude Afif, Issam I RaadAbstract:BACKGROUND. Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with Hematologic Malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS. The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n = 106) or ABLC (n = 52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the Hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS. Risk factors for IA, such as underlying Malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7–15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P < .001). CONCLUSIONS. Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting. Cancer 2008. © 2008 American Cancer Society.
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posaconazole as salvage treatment for invasive fusariosis in patients with underlying Hematologic Malignancy and other conditions
Clinical Infectious Diseases, 2006Co-Authors: Issam I Raad, Ray Y Hachem, Raoul Herbrecht, John R. Graybill, Roberta S. Hare, Gavin Corcoran, Dimitrios P. KontoyiannisAbstract:Background. Conventional amphotericin B–based antifungal therapy for invasive fusariosis in patients with a Hematologic Malignancy results in a 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. Methods. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. Results. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for 13 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. Conclusion. These results suggest that posaconazole is useful for the treatment of invasive fusariosis. After Aspergillus species, Fusarium species are among the leading fungal pathogens to cause invasive mold infection in patients with underlying Hematologic Malignancy and in those who have undergone hematopoietic stem cell transplantation (HSCT) [1–3]. Mortality rates associated with fusariosis have equaled or exceeded 70% [2, 4], and progression in high-risk patients is often fulminant, leaving a narrow window of opportunity for therapeutic intervention. The primary antifungal therapy is amphotericin B or its lipid formulations [2, 5, 6]; however, this therapy is of limited efficacy because of its potential toxicity and poor activity against Fusarium organisms in vivo. Other treatment options include voriconazole, which is indicated for the treatment of fusariosis in patients intolerant of or with disease refractory to other therapy.
Lee Ann Baxterlowe - One of the best experts on this subject based on the ideXlab platform.
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optimal donor for african americans with Hematologic Malignancy hla haploidentical relative or umbilical cord blood transplant
Biology of Blood and Marrow Transplantation, 2020Co-Authors: Scott R Solomon, Lee Ann Baxterlowe, Claudio G. Brunstein, Meijie Zhang, Karen K Ballen, Andrew St Martin, Asad Bashey, Minoo Battiwalla, Saurabh ChhabraAbstract:ABSTRACT Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for Hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with Hematologic Malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P
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impact of allele level hla matching on outcomes after myeloablative single unit umbilical cord blood transplantation for Hematologic Malignancy
Blood, 2014Co-Authors: Mary Eapen, John P Klein, Annalisa Ruggeri, Stephen R Spellman, Stephanie J Lee, Claudio Anasetti, William Arcese, Juliet N Barker, Lee Ann BaxterloweAbstract:We studied the effect of allele-level matching at human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for Hematologic Malignancy. The primary end point was nonrelapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset, allele-level HLA match was assigned using imputation; concordance between HLA-match assignment and outcome correlation was confirmed between the actual and imputed HLA-match groups. Compared with HLA-matched units, neutrophil recovery was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles. NRM was higher with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLA-matched units. The observed effects are independent of cell dose and patient age. These data support allele-level HLA matching in the selection of single UCB units.
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effect of hla matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for Hematologic Malignancy
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Vanderson Rocha, Annalisa Ruggeri, Stephen R Spellman, Lee Ann Baxterlowe, Meijie Zhang, Duncan Purtill, Colleen Brady, Etienne Baudoux, Paola Bergamaschi, Robert ChowAbstract:Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non–NIMA-matched UCBTs. All patients had a Hematologic Malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs ( P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.
Ray Y Hachem - One of the best experts on this subject based on the ideXlab platform.
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granulocyte transfusions in Hematologic Malignancy patients with invasive pulmonary aspergillosis outcomes and complications
Annals of Oncology, 2013Co-Authors: Issam I Raad, Anne Marie Chaftari, M Al M Shuaibi, Ying Jiang, William Shomali, Jorge E Cortes, Benjamin Lichtiger, Ray Y HachemAbstract:Abstract Background Granulocyte transfusions (GTXs) have been used successfully as an adjunctive treatment option for invasive infections in some neutropenic patients with underlying Hematologic Malignancy (HM). Patients and methods We sought to determine the impact of GTX as an adjunct to antifungal therapy in 128 patients with HM and prolonged neutropenia (≥14 days) with a proven or probable invasive aspergillosis (IA) infection by retrospectively reviewing our institutional database. Results Fifty-three patients received GTX and 75 did not. By univariate analysis, patients with invasive pulmonary aspergillosis who received GTX were less likely to respond to antifungal therapy (P = 0.03), and more likely to die of IA (P = 0.009) when compared with the non-GTX group. Among patients who received GTX, 53% developed a pulmonary reaction. Furthermore, IA-related death was associated with the number of GTX given (P = 0.018) and the early initiation of GTX within 7 days after starting antifungal therapy (P = 0.001). By multivariate competing risk analysis, patients who received GTX were more likely to die of IA than patients who did not receive GTX (P = 0.011). Conclusions Our study suggests that GTX does not improve response to antifungal therapy and is associated with worse outcomes of IA infection in HM patients, particularly those with pulmonary involvement.
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utility of galactomannan enzyme immunoassay and 1 3 β d glucan in diagnosis of invasive fungal infections low sensitivity for aspergillus fumigatus infection in Hematologic Malignancy patients
Journal of Clinical Microbiology, 2009Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Roy F Chemaly, Yunfang Jiang, Ruth Reitzel, Issam I RaadAbstract:Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in Hematologic Malignancy patients.
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amphotericin b lipid complex versus liposomal amphotericin b monotherapy for invasive aspergillosis in patients with Hematologic Malignancy
Cancer, 2008Co-Authors: Ray Y Hachem, Dimitrios P. Kontoyiannis, Hend Hanna, Maha Boktour, Rola Husni, Harrys A Torres, Claude Afif, Issam I RaadAbstract:BACKGROUND. Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with Hematologic Malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS. The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n = 106) or ABLC (n = 52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the Hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS. Risk factors for IA, such as underlying Malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7–15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P < .001). CONCLUSIONS. Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting. Cancer 2008. © 2008 American Cancer Society.
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posaconazole as salvage treatment for invasive fusariosis in patients with underlying Hematologic Malignancy and other conditions
Clinical Infectious Diseases, 2006Co-Authors: Issam I Raad, Ray Y Hachem, Raoul Herbrecht, John R. Graybill, Roberta S. Hare, Gavin Corcoran, Dimitrios P. KontoyiannisAbstract:Background. Conventional amphotericin B–based antifungal therapy for invasive fusariosis in patients with a Hematologic Malignancy results in a 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. Methods. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. Results. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for 13 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. Conclusion. These results suggest that posaconazole is useful for the treatment of invasive fusariosis. After Aspergillus species, Fusarium species are among the leading fungal pathogens to cause invasive mold infection in patients with underlying Hematologic Malignancy and in those who have undergone hematopoietic stem cell transplantation (HSCT) [1–3]. Mortality rates associated with fusariosis have equaled or exceeded 70% [2, 4], and progression in high-risk patients is often fulminant, leaving a narrow window of opportunity for therapeutic intervention. The primary antifungal therapy is amphotericin B or its lipid formulations [2, 5, 6]; however, this therapy is of limited efficacy because of its potential toxicity and poor activity against Fusarium organisms in vivo. Other treatment options include voriconazole, which is indicated for the treatment of fusariosis in patients intolerant of or with disease refractory to other therapy.
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Posaconazole as Salvage Treatment for Invasive Fusariosis in Patients with Underlying Hematologic Malignancy and Other Conditions
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2006Co-Authors: Issam I Raad, Ray Y Hachem, Raoul Herbrecht, John R. Graybill, Roberta S. Hare, Gavin Corcoran, Dimitrios P. KontoyiannisAbstract:Conventional amphotericin B-based antifungal therapy for invasive fusariosis in patients with a Hematologic Malignancy results in a > or = 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for >3 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. These results suggest that posaconazole is useful for the treatment of invasive fusariosis.