Extramedullary (EM) plasmacytomas (EMPs) that are not progression of intramedullary (IM) plasma cell myeloma (PCM) are usually indolent. In contrast, EM spread of IM PCM is associated with a poor ...prognosis. The recently introduced Durie-Salmon PLUS staging system includes EM disease in the poor prognosis category. One study noted an increase in EM disease both at diagnosis and during follow-up of PCM in 2000-2007 compared with previous years raising concerns that adoption of novel agents (thalidomide, lenalidomide and bortezomib) and greater use of hematopoietic cell transplantation (HCT) might be contributory to this. It is uncertain if this is a true increase or merely greater detection due to the increasing use of more sensitive imaging techniques (computerized tomography, magnetic resonance imaging and ¹⁸F-fluorodeoxyglucose positron emission tomography) or a reflection of the evolving natural history of PCM in an era when patients are living longer (median overall survival before 1996 was 29.9 months vs 44.8 months after 1996). Recent studies suggest there are important biological differences between PCM with or without EM spread that are offering clues that might explain the propensity for dissemination and a more aggressive clinical course. For example, EM relapse in PCM with and without deletion 13 was 30.8 vs 5.6%, suggesting the biology of a plasma cell subclone before HCT can affect the nature of the relapse after HCT. This article will explore the clinical, biological and treatment implications of EM spread of PCM. In addition, the impact of extramedullary disease on the outcomes of autologous and allogeneic HCT for PCM will be analyzed. Allogeneic HCT early in the course of high-risk PCM with EM disease is a consideration since graft vs myeloma effects may be essential to achieve maximal survival benefits.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this double-blind study to compare safety of 2 lipid formulations of amphotericin B, neutropenic patients with unresolved fever after 3 days of antibacterial therapy were randomized (1 : 1 : 1) to ...receive amphotericin B lipid complex (ABLC) at a dose of 5 mg/kg/d (n = 78), liposomal amphotericin B (L Amph) at a dose of 3 mg/kg/d (n = 85), or L Amph at a dose of 5 mg/kg/d (n = 81). L Amph (3 mg/kg/d and 5 mg/kg/d) had lower rates of fever (23.5% and 19.8% vs. 57.7% on day 1; P < .001), chills/rigors (18.8% and 23.5% vs. 79.5% on day 1; P < .001), nephrotoxicity (14.1% and 14.8% vs. 42.3%; P < .01), and toxicity-related discontinuations of therapy (12.9% and 12.3% vs. 32.1%; P = .004). After day 1, infusional reactions were less frequent with ABLC, but chills/rigors were still higher (21.0% and 24.3% vs. 50.7%; P < .001). Therapeutic success was similar in all 3 groups.
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Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic ...hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n=72) or fusariosis (n=52) between days 0 and 365 after HCT are described and compared with a control cohort (n=11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P=0.004) and were more likely to have a Karnofsky performance status (KPS) <90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P=0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P<0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Umbilical cord blood (UCB) is an attractive stem cell graft option for patients who need allogeneic hematopoietic stem cell support, but lack a suitable HLA-matched donor. However, the limited number ...of hematopoietic progenitor cells in a single cord blood unit can lead to an increased risk of graft failure, delayed hematological recovery and prolonged immunosuppression, particularly in adult patients. Several strategies to overcome these potential limitations are being evaluated. In this review, we discuss promising ex vivo manipulations to enhance cord blood engraftment capacity such as culture of UCB cells with stimulatory cytokines and growth factors, mesenchymal cells, Notch ligand, copper chelators, prostaglandins, complement components, nicotinamide and CD26/DPPIV inhibitors. All these approaches are now in early clinical trials. However, despite the fact that several cord blood enhancement strategies have resulted in increased numbers of progenitor cells and faster neutrophil recovery, the ability of these techniques to significantly shorten engraftment time and permit the use of cord units with low numbers of total nucleated cells, or accomplish reliable engraftment with a single cord, have yet to be convincingly demonstrated. The ultimate clinical value of ex vivo cord blood expansion or manipulation has not been defined yet, and the current data do not permit predicting which technology will prove to be the optimal strategy. Nevertheless, expectations remain high that eventually ex vivo enhancement will be able to improve clinical outcomes and significantly extend the applicability of UCB transplantation.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A number of surveys have documented increased rates of candida infection over the past several decades. In this assessment of the frequency and distribution of non-albicans Candida species among ...patients with cancer, 37 reports that were published between 1952 and 1992 and that described 1,591 cases of systemic candida infection were reviewed. Species other than Candida albicans accounted for 46% of all systemic candida infections in patients with cancer; specifically, Candida tropicalis accounted for 25%, Candida glabrata for 8%, Candida parapsilosis for 7%, and Candida krusei for 4%. Other species were uncommon. C. tropicalis was the predominant pathogenic Candida species in five reports, C. glabrata in two, C. krusei in two, and Candida stellatoidea in one. The perception that, over time, a greater proportion of candida infections have been caused by non-albicans species was not borne out. The wide variability in reported findings was striking and was due in part to differences in the underlying diseases affecting the patients described. For example, patients with leukemia were more likely to be infected by C. albicans or C. tropicalis but less likely to be infected by C. glabrata than patients with other types of cancer. The recent increase in the rate of bone marrow transplantation may also have contributed to discrepancies among reports. Bone marrow transplant recipients were more likely to be infected by C. krusei or C. lusitaniae. The other factors partially responsible for the variability among reports included common-source contamination and the pressures imposed by antimicrobial measures.
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Bacteria remain an important cause of infection in bone marrow transplants. To examine shifts in the etiology and susceptibility of bacterial isolates from transplants, we reviewed the incidence and ...susceptibility of blood isolates during a 7-year period. The infection rate fell dramatically during this time. Gram-positive organisms were isolated more often than gram-negative organisms, but the trend is reversing. Streptococci surpassed staphylococci for 5 years as the leading pathogen. Increasing resistance to penicillin, ciprofloxacin, and imipenem was noted in Streptococcus species. With the exception of type 1 β-lactamase-producing bacteria and Pseudomonas aeruginosa, gram-negative isolates remained overall susceptible to ceftazidime. Increased antibiotic prophylaxis coincided with the reduction in percentage of infected patients and increase in resistance to β-lactam antibiotics. Mortality attributed to bacteremia was low except for infections caused by P. aeruginosa and the Enterobacter, Serratia, Citrobacter group. There was no mortality attributable to gram-positive organisms such as Staphylococcus aureus and viridans streptococci.
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Allogeneic bone marrow transplantation is an effective therapy for various types of leukemia and aplastic anemia.
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It has the potential to cure acute leukemia in patients whose disease does not or ...probably will not respond to conventional treatment.
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It is the only known cure for chronic myelogenous leukemia (CML)
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and is the most effective therapy for severe aplastic anemia in young patients.
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Initially limited to use in patients who had an HLA-identical sibling donor, bone marrow transplantation is now an option for many more patients, since marrow from unrelated
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or HLA-mismatched related
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donors may be used and since . . .
Physician practice variation may be a barrier to informing hematopoietic cell transplant (HCT) recipients about fertility preservation (FP) options. We surveyed HCT physicians in the United States to ...evaluate FP knowledge, practices, perceptions and barriers. Of the 1035 physicians invited, 185 completed a 29-item web-survey. Most respondents demonstrated knowledge of FP issues and discussed and felt comfortable discussing FP. However, only 55% referred patients to an infertility specialist. Most did not provide educational materials to patients and only 35% felt that available materials were relevant for HCT. Notable barriers to discussing FP included perception that patients were too ill to delay transplant (63%), patients were already infertile from prior therapy (92%) and time constraints (41%). Pediatric HCT physicians and physicians with access to an infertility specialist were more likely to discuss FP and to discuss FP even when prognosis was poor. On analyses that considered physician demographics, knowledge and perceptions as predictors of referral for FP, access to an infertility specialist and belief that patients were interested in FP were observed to be significant. We highlight variation in HCT physician perceptions and practices regarding FP. Physicians are generally interested in discussing fertility issues with their patients but lack educational materials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains a principal cause of infectious mortality after bone marrow transplantation (BMT). We reviewed the medical records of ...93 allogeneic and 149 autologous transplant recipients during a 20 month period, with attention to cases of proven or probable IA. No autologous transplant recipient developed IA, whereas IA was seen in 15.1% of allogeneic recipients (including two of five patients with a prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The median time to occurrence was 92 days post transplant, with no de novo cases developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk factors for the development of IA included > or = 21 days of corticosteroid therapy of >or= 1mg/kg/day and post-transplant cytomegalovirus (CMV) infection. These two risk factors were statistically linked. Our data illustrate a shift toward a later occurrence of post-transplant IA, suggesting a need for close, prolonged surveillance in the outpatient environment. The contributory role of protracted corticosteroid use is also highlighted. These data have important implications in an era of alternate donor transplants and more intense immunosuppression. Established strategies implementing newer, less toxic antifungal agents as prophylaxis in high-risk patients are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background. Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical ...studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results. The revised definitions retain the original classifications of “proven,” “probable,” and “possible” invasive fungal disease, but the definition of “probable” has been expanded, whereas the scope of the category “possible” has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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