|
| ||
|
|
||
Cell Transplant (cell + transplant)
Kinds of Cell Transplant Terms modified by Cell Transplant Selected Abstracts,-Endorphin Neuronal Cell Transplant Reduces Corticotropin Releasing Hormone Hyperresponse to Lipopolysaccharide and Eliminates Natural Killer Cell Functional Deficiencies in Fetal Alcohol Exposed RatsALCOHOLISM, Issue 5 2009Nadka I. Boyadjieva Background:, Natural killer (NK) cell dysfunction is associated with hyperresponse of corticotropin releasing hormone (CRH) to immune challenge and with a loss of ,-endorphin (BEP) neurons in fetal alcohol exposed animals. Recently, we established a method to differentiate neural stem cells into BEP neurons using cyclic adenosine monophosphate (cAMP)-elevating agents in cultures. Hence, we determined whether in vitro differentiated BEP neurons could be used for reversing the compromised stress response and immune function in fetal alcohol exposed rats. Methods:, To determine the effect of BEP neuron transplants on NK cell function, we implanted in vitro differentiated BEP neurons into the paraventricular nucleus of pubertal and adult male rats exposed to ethanol or control in utero. The functionality of transplanted BEP neurons was determined by measuring proopiomelanocortin (POMC) gene expression in these cells and their effects on CRH gene expression under basal and after lipopolysaccaride (LPS) challenge. In addition, the effectiveness of BEP neurons in activating NK cell functions is determined by measuring NK cell cytolytic activity and interferon-, (IFN-,) production in the spleen and in the peripheral blood mononuclear cell (PBMC) following cell transplantation. Results:, We showed here that when these in vitro differentiated BEP neurons were transplanted into the hypothalamus, they maintain biological functions by producing POMC and reducing the CRH neuronal response to the LPS challenge. BEP neuronal transplants significantly increased NK cell cytolytic activity in the spleen and in the PBMC and increased plasma levels of IFN-, in control and fetal alcohol exposed rats. Conclusions:, These data further establish the BEP neuronal regulatory role in the control of CRH and NK cell cytolytic function and identify a possible novel therapy to treat stress hyperresponse and immune deficiency in fetal alcohol exposed subjects. [source] Eradication of Multiple Myeloma and Breast Cancer Cells by TH9402-mediated Photodynamic Therapy: Implication for Clinical Ex Vivo Purging of Autologous Stem Cell Transplants,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2000N. Brasseur ABSTRACT High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1,2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5,10 ,M dye followed by a 90 min washout period and a light dose of 5,10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 × 106 cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. [source] The chemotaxis defect of Shwachman-Diamond Syndrome leukocytesCYTOSKELETON, Issue 3 2004Vesna Stepanovic Abstract Shwachman-Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer-assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158,174, 2004. © 2004 Wiley-Liss, Inc. [source] The clinical and epidemiological burden of chronic lymphocytic leukaemiaEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2004A. REDAELLI phd director of global outcomes research-oncology The purpose of this literature review was to identify and summarize published studies describing the epidemiology and management of chronic lymphocytic leukaemia (CLL). Chronic lymphocytic leukaemia represents 22,30% of all leukaemia cases with a worldwide incidence projected to be between <,1 and 5.5 per 100 000 people. Australia, the USA, Ireland and Italy have the highest CLL incidence rates. Chronic lymphocytic leukaemia presents in adults, at higher rates in males than in females and in whites than in blacks. Median age at diagnosis is 64,70 years. Five-year survival rate in the USA is 83% for those <,65 years old and 68% for those 65 + years old. Hereditary and genetic links have been noted. Persons with close relatives who have CLL have an increased risk of developing it themselves. No single environmental risk factor has been found to be predictive for CLL. Patients are usually diagnosed at routine health care visits because of elevated lymphocyte counts. The most common presenting symptom of CLL is lymphadenopathy, while difficulty exercising and fatigue are common complaints. Most patients do not receive treatment after initial diagnosis unless presenting with clear pathologic conditions. Pharmacological therapy may consist of monotherapy or combination therapy involving glucocorticoids, alkylating agents, and purine analogs. Fludarabine may be the most effective single drug treatment currently available. Combination therapy protocols have not been shown to be more effective than fludarabine alone. As no cure is yet available, a strong unmet medical need exists for innovative new therapies. Experimental treatments under development include allogeneic stem cell transplant, mini-allogeneic transplants, and monoclonal antibodies (e.g. alemtuzumab against CD52; rituximab against CD20). [source] Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Anna Candoni Abstract Introduction:,WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT). Methods and results:, The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454,13923) copies WT1/104Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available). Conclusions:, In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT-PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non-specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy. [source] Invasive fungal infections in patients with acute myeloid leukemia and in those submitted to allogeneic hemopoietic stem cell transplant: who is at highest risk?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008Morena Caira No abstract is available for this article. [source] Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paperEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008M. Dungarwalla Abstract Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [source] Decreasing mortality from non-Hodgkin lymphoma in AustraliaINTERNAL MEDICINE JOURNAL, Issue 12 2008M. Coory Abstract Based on the number of new cases (incidence), non-Hodgkin lymphoma is an increasingly common cancer in Australia and many developed countries. Until recently, mortality trends have been stable or slightly increasing. However, since the year 2000, mortality has decreased every year by an average of 5.1% per year (95% confidence interval (CI) ,7.1 to ,3.1%), whereas incidence has continued to increase at 0.9% per year (95%CI 0.6 to 1.2%). It was not possible with the population-based registry data available to us to untangle the causes of the decrease in mortality. The stable mortality rates during the 1990s (in the face of increasing incidence) might have been because of introduction of novel therapies such as autologous stem cell transplant for relapsed diffuse large cell lymphoma or the purine analogue-based therapy for indolent lymphomas. A plausible explanation for the large decrease in mortality since 2000 is the introduction of the monoclonal antibody rituximab. [source] Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantationINTERNAL MEDICINE JOURNAL, Issue 9 2006A. B. D'Souza Abstract Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T -score < ,2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was ,13% (range, ,51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, ,20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was ,13.2% (range, ,40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, ,22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was ,12.5% (range, ,38 to +6.9%). Post-ZA, spinal BMD decreased by a median of ,2.8% (range, ,27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study. [source] Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patientsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2008Shinichi Imafuku MD Background, Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. Methods, To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Results, Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann,Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. Conclusions, In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms. [source] Nonmyeloablative peripheral blood stem cell transplant for T-cell prolymphocytic leukaemia complicated by fulminant haemolysis and acute renal failure at engraftment secondary to minor ABO incompatibilityINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2005N. J. CURTIN Summary We present a 54-year-old man who underwent human leucocyte antigen-identical sibling nonmyeloablative peripheral blood stem cell transplant for primary refractory T-cell prolymphocytic leukaemia (T-PLL). His clinical course was complicated by fulminant haemolysis and acute renal failure at the time of engraftment because of minor ABO incompatibility between the donor and the recipient. This case highlights the curative potential of nonmyeloablative transplantation for T-PLL as well as the potential severity of immune haemolysis secondary to minor ABO incompatibility. [source] Management of systemic lupus erythematosus in the coming decade: potentials and challengesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2006Hiok Hee CHNG Abstract The management of systemic lupus erythematosus (SLE) has improved in the past 50 years, but there is still a 3,5-fold increased mortality compared to the general population, with major organ failure due to active disease, infection and cardiovascular disease as the major challenges for the coming decade. Research advances at cellular, molecular and genetic levels enhance our understanding of the immunopathogenic mechanisms of SLE, leading to the development of drugs targeting specific sites of immune dysregulation , with therapies directed at cytokines, B- and T-cells, and their interactions showing promise. Advances are expected in the field of haematopoietic stem cell transplant (HSCT) as a therapeutic option for a subset of patients. Furthermore, some non-traditional immunomodulating therapies like statins, leflunomide and tacrolimus may prove useful as alternative or adjunct treatment in some patients. A better understanding of how current immunosuppressants act at the cellular and molecular level should guide the re-evaluation of the indications, doses and duration of therapy in clinical trials using these agents, many of which have not been subjected to proper double-blinded placebo-controlled studies. Research on triggers of SLE onset and flare of activity continues to yield information helpful in prevention. The evidence on the impact of psychosocial and economic factors on the outcome of SLE is overwhelming and the rheumatology community should enlist the assistance of other healthcare professionals, patient advocates and local health authorities to address these issues pertinent to good patient care and outcome. [source] Keratinocyte Dysplasia in Hematopoietic Stem Cell Transplant Recipients in the Day 28 to 84 Post Transplant Period.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005Ning Li MD Severe keratinocyte dysplasia (SKD) has been reported in the early post-transplant period of hematopoietic stem cell transplant (HCST) patients, with a frequency as high as 47.4%. In the period less than 3 weeks post-transplant it was associated with cyclophosphamide conditioning. The purpose of our study was to determine the prevalence of SKD in a later post-transplant period, from 28 days to 84 days, and study the possible causes. The 2003 slide file (227 slides) of Seattle Cancer Care Alliance was examined for skin biopsies from patients who had undergone HCST. Twenty-two cases (9.7%) showed SKD. A control group of 22 biopsies matched for days post-transplant and age were selected from the remaining 205 biopsies. SKD was associated with a busulfan conditioning regimen, 72.7% in the SKD group and 36.3% in the control group (p = 0.016). SKD was not associated with cyclophosphamide (p = 0.174), fludarabin (p = 0.263) or total body irradiation (p = 0.50). Although active GVHD (grade 2 or 3) was more commonly seen in SKD group (45.5%) than the control group (22.2%), it did not show significant difference (p = 0.052). Our study showed that SKD developed in 9.7% of the skin biopsies from days 28 to 84 post-transplant, and was associated with busulfan conditioning regimen. [source] Quantitative temporal and spatial distribution of adenovirus type 2 correlates with disease manifestations and organ failure during disseminated infectionJOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Dirk Forstmeyer Abstract Disseminated adenovirus (HAdV) infections are serious complications in allogenic stem cell transplant (SCT) recipients. Quantitative HAdV DNA detection in blood samples demonstrated the association of high virus loads with disease and improved early diagnosis. However, the pathogenesis of disseminated HAdV disease, for example sources of HAdV DNA shedding in the blood stream and association of HAdV replication sites with disease manifestations, remained obscure. In this report, 24 bioptic and autoptic organ and tissue samples of an adult SCT recipient suffering from disseminated infection were quantitatively analyzed for HAdV DNA. Results indicate subsequent virus replication in the colon, bone marrow and liver as origin of HAdV DNAemia, which increased from 1.4,×,104 copies/ml to a peak of 2,×,109 copies/ml over a period of 84 days in spite of antiviral therapy. Symptoms as diarrhoea, bone marrow failure and hepatic failure were clearly linked to high HAdV DNA concentrations in affected organs. For example, the HAdV DNA level was 2.2,× 103 copies/cell in a colon biopsy when the patient suffered from diarrhoea whereas only 1.1,× 101 copies/cell were detected when symptoms had improved. Focal HAdV infection of the liver as demonstrated by laser microdissection was followed by fulminant virus replication with 1.3,×,105 copies of HAdV DNA/cell causing terminal hepatic failure. In conclusion, pathogenesis of disseminated HAdV disease was associated with virus replication in affected organs and not immune mediated as suggested recently by a fatal case of gene therapy with a non-replication competent HAdV-C5 vector. J. Med. Virol. 80:294,297, 2008. © 2007 Wiley-Liss, Inc. [source] Ten Years' Experience of Antenatal Mean Corpuscular Volume Screening and Prenatal Diagnosis for Thalassaemias in Hong KongJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2000Dr. S. Y. Sin Abstract Objective: To determine the prevalence of thalassaemia carriers in Hong Kong. Subjects and Methods: From 1988 to 1997, 25834 (53.7%) of 48089 mothers were screened for thalassaemias by mean corpuscular volume (MCV) at the first antenatal visit. Results: In the screened population of 25834, 2229 (8.6%) had MCV , 75 fl. Of these, 1121 (4.3%) were ,-thal, 715 (2.8%) were ,-thal, 23 (0.1%) were ,,-thal, 57 (0.2%) were other haemoglobin variants, and 281 (1.1%) had either iron deficiency or uncertain causes. Out of 200 pregnancies at risk for homozygous ,-thal-1 and 32 at risk for ,-thal major, 27 homozygous ,-thal-1 and 7 ,-thal major were identified, compared favourably with the expected figures of 23 and 9. Conclusion: Antenatal screening for thalassaemias by MCV is simple, effective and reliable. Universal screening has a different impact as bone marrow or cord blood stem cell transplant provides cure for ,-thal major. At risk couples have, as an alternative to termination of pregnancy, the option of early detection and treatment for their affected newborns or fetuses. [source] Review article: management of hepatic disease following haematopoietic cell transplantALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006G. B. McDONALD Summary Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug-induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant. Pre-transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes. This review covers pre-transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long-term survivors. [source] Successful treatment of pulmonary zygomycosis in two transplant recipients with liposomal amphotericin B and partial surgical resection followed by posaconazoleMYCOSES, Issue 2 2010David T. Cooke Summary Pulmonary zygomycosis is a relatively uncommon complication of solid organ or peripheral blood stem cell transplantation and has a high associated mortality. Optimal therapy consists of complete resection of infected tissue and treatment with amphotericin B (AmB). We describe two patients, one of whom underwent orthotopic heart transplantation and the other who received a peripheral blood stem cell transplant, who were diagnosed with invasive pulmonary zygomycosis. Both patients were treated with a liposomal preparation of AmB and early partial resection of the infected structures followed by prolonged posaconazole maintenance therapy. Despite incomplete resection, this treatment regimen resulted in a favourable outcome in both patients, including survival of more than 17 months in one patient at last follow up. For patients in whom complete resection of pulmonary zygomycosis is not possible, subtotal resection and treatment with liposomal AmB followed by therapy with posaconazole may be an effective treatment option. [source] Oral graft-versus-host diseaseORAL DISEASES, Issue 5 2008MM Imanguli Objective:, Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in patients receiving hematopoietic cell transplant. It is estimated that 40,70% of engrafted patients surviving the initial transplant eventually develop chronic GVHD (cGVHD), which can persist for months to years and require long-term management from multiple disciplines. This review describes the oral component of this transplant complication. Design:, The search related to GVHD patho-biology, salivary gland disease after hematopoietic cell transplant and treatments for oral GVHD encompassed literature from 1966 through 2008. Searches were limited to the MEDLINE/PubMed database and English language literature in peer-reviewed journals. Results:, Our understanding of the patho-biology of oral cGVHD is based on studies of other affected tissues. It is difficult to determine the prevalence and incidence of salivary gland disease after transplant because there is no universally accepted case definition. In general, clinical trials for treatment of oral cGVHD have been too small to make strong recommendations for use in clinical practice. Conclusions:, Larger well-designed clinical studies are needed to understand the patho-biology of oral cGVHD and determine best treatments for this disease. [source] Necrosis following skull base irradiation and stem cell transplant for multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Sonia Skamene No abstract is available for this article. [source] A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Patrick B. Johnston Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27,68). Patients had received a median of six prior therapies (range, 3,14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24,71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Liver function tests and absolute lymphocyte count at day +100 are predictive factors for extensive and severe chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Fernando Silva First page of article [source] Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009Mike G. Martin The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m2 on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18,70) and 47 years (range 20,68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Severity of health conditions identified in a pediatric cancer survivor program,PEDIATRIC BLOOD & CANCER, Issue 7 2010Karen Wasilewski-Masker MD Abstract Background The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was designed for reporting acute and late effects of cancer treatment. To date, no study of pediatric-aged cancer survivors has graded health conditions using CTCAE, for patients in active follow-up in a cancer survivor program. Procedure Medical records were reviewed on 519 survivors of non-central nervous system childhood malignancies seen in the Cancer Survivor Program between January 1, 2001 and December 15, 2005. Health problems identified through histories, physicals, and recommended evaluation using the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancer were graded using the CTCAE. Results Overall, 1,625 adverse health conditions were reported or detected in 519 pediatric-age cancer survivors (mean age at diagnosis 4.8 years; mean age at first survivor visit 12.1 years). The majority of conditions were mild (47.4% Grade 1) or moderate (35.2% Grade 2); however, 17.4% of conditions were severe (Grade 3) or life-threatening/disabling (Grade 4). Only 12.1% of survivors had no adverse condition, and 36.2% of survivors had a Grade 3 or 4 condition. In a Cox multivariate analysis risk factors for a Grade 3 or 4 condition included minority race, diagnosis of other malignancy, older age, and a history of a hematopoietic stem cell transplant. Conclusions The majority of adverse health conditions in pediatric-aged cancer survivors are mild; however, a significant percentage will have a serious condition. Long-term follow-up with a multidisciplinary approach is essential to detect and intervene in health problems early. Pediatr Blood Cancer 2010;54:976,982 © 2010 Wiley-Liss, Inc. [source] Reduced intensity and non-myeloablative allogeneic stem cell transplantation in children and adolescents with malignant and non-malignant diseasesPEDIATRIC BLOOD & CANCER, Issue 1 2008Prakash Satwani MD Abstract Allogeneic hematopoietic stem cell transplant (AlloSCT) from related or unrelated histocompatible donors has been well established as potentially curative therapy for children and adolescents with selected malignant and non-malignant diseases. In the malignant setting non-myeloablative (NMA)/reduced intensity (RI)-AlloSCT eradicates malignant cells through a graft versus malignancy effect provided by alloreactive donor T-lymphocytes and/or natural killer cells. In patients with non-malignant diseases NMA/RI AlloSCT provides enough immunosuppression to promote engraftment and correct underlying genetic defects. In children, myeloablative AlloSCT is not only associated with acute short-term toxicities but also long-term late complications such as growth retardation, infertility, and secondary malignancies. NMA/RI-AlloSCT in children may be associated with reduction in use of blood products, risk of infections, transplant-related mortality, and length of hospitalization. Despite the success of RI-AlloSCT in adults, large prospective and/or randomized multicenter studies are necessary in children and adolescent recipients to define the appropriate patient population, optimal conditioning regimens, cost-benefits, survival and differences in short-term and long-term effects compared to conventional myeloablative conditioning. Pediatr Blood Cancer 2008;50:1,8. © 2007 Wiley-Liss, Inc. [source] Failure of intravenous pentamidine prophylaxis to prevent pneumocystis pneumonia in a pediatric hematopoietic stem cell transplant (HSCT) patientPEDIATRIC BLOOD & CANCER, Issue 6 2006Aaron M. Milstone MD No abstract is available for this article. [source] Pulmonary function in long-term survivors of pediatric hematopoietic cell transplantationPEDIATRIC BLOOD & CANCER, Issue 5 2006Paul A. Hoffmeister MPH Abstract Background The purpose of this study was to determine the prevalence of pulmonary dysfunction in pediatric hematopoietic cell transplant (HCT) survivors and to identify associated risk factors. Procedure In a cross-sectional study, patients surviving at least 5 years after pediatric HCT were requested to undergo pulmonary function testing (PFT). Risk factors for restrictive lung disease (RLD) and obstructive lung disease (OLD) were analyzed using multivariate analysis. Results Among 472 patients contacted, 260 (55%) participated and 215 were selected for analysis. These patients were transplanted at a median age of 8.3 (0.3,18.0) years; 175 for hematologic malignancies and 40 for non-malignant diseases. The preparative regimens for 133 patients included fractionated TBI (FTBI), 29 single-fraction TBI (SFTBI), and 53 non-TBI regimens. PFT was performed at a median of 10 (5.0,27.5) years after HCT. Forty percent of patients had either RLD or OLD (28% RLD, 9% OLD, 3% mixed RLD/OLD) and at least 15% had an isolated low-DLCO. Moderate-to-severe impairment was present in 45% of patients with RLD or OLD. In multivariate analysis, risk factors associated with RLD included transplant regimen, transplant diagnosis, scleroderma/contracture, and donor relation. Patients treated with SFTBI had the highest risk of RLD. Risk factors for OLD included chronic graft-versus-host disease, transplant regimen, and time after HCT. Patients surviving 20 or more years after HCT had the highest risk of OLD. Conclusions Fifty-five percent of long-term pediatric HCT survivors had pulmonary dysfunction. These findings stress the need for long-term follow-up to detect pulmonary dysfunction. Pediatr Blood Cancer 2006; 47:594,606. © 2005 Wiley-Liss, Inc. [source] Long-term complications in survivors of advanced stage neuroblastoma,PEDIATRIC BLOOD & CANCER, Issue 3 2005Caroline Laverdière MD Abstract Background Few studies have assessed late effects in neuroblastoma (NB) survivors, particularly those with advanced stage disease. Methods Retrospective analysis of a cohort of advanced stage NB survivors followed in a late effect clinic at a single institution. Screening tests to detect late effects were tailored depending on the individual's treatment exposures. Results The study included 63 survivors (31 males). The median age at diagnosis was 3.0 years. The median follow-up from diagnosis was 7.06 years. All patients had surgery and received chemotherapy, 89% received radiation therapy (RT), 62% immunotherapy, and 56% autologous stem cell transplant. Late complications were detected in 95% of survivors and included: hearing loss (62%), primary hypothyroidism (24%), ovarian failure (41% of females), musculoskeletal (19%), and pulmonary (19%) abnormalities. The majority of complications were moderate, with only 4% being life-threatening. Survivors who received cisplatin were at greater risk to develop hearing loss compared to those not so treated (OR 9.74; 95% CI: 0.9,101.6). A total dose of cyclophosphamide greater than 7.4 g was associated with ovarian failure (P,=,0.02). Conclusions Late complications occur frequently in survivors of advanced stage NB. The majority of these problems are of mild-moderate severity. Long-term follow-up (LFTU) and screening of this population is essential. © 2005 Wiley-Liss, Inc. [source] Early bacteremia in pediatric hematopoietic stem cell transplant patients on oral antibiotic prophylaxisPEDIATRIC BLOOD & CANCER, Issue 2 2005Leslie S. Kersun MD, MSCE Abstract Background Bacteremia occurs during hematopoietic stem cell transplant (HSCT) in 20%,25% of patients and the use of gut decontamination (GD) to decrease this risk is controversial. Our purpose was to determine the incidence of bacteremia and antimicrobial resistance post-HSCT in pediatric patients receiving GD, and to identify risk factors associated with infection. Procedures This was a retrospective cohort study of 182 pediatric patients undergoing first HSCT for malignant disease at The Children's Hospital of Philadelphia from January, 1999 to December, 2002. We examined the impact of age, sex, race, diagnosis, disease status, conditioning regimen, recent bacteremia, stem cell source, donor, graft versus host disease prophylaxis agents, and mucositis severity using Cox proportional hazard models. GD consisted of amoxicillin (azithromycin, if penicillin allergic) and oral gentamicin. Outcome was first episode of bacteremia prior to absolute neutrophil count (ANC) 500/mm3. Antibiotic susceptibilities were performed on all isolates. Results Seventy-four patients (41%) developed bacteremia. The majority were Gram-positive cocci, with Staphylococcal (50%) and Streptococcal species (28%) the most common. Gram-negative organisms were identified in 22% with Pseudomonas (5.7%) and Klebsiella species (3.4%) the most common. Of the Streptococcal infections, 72% were resistant to ampicillin; only 25% of the Gram-negative bacteria were resistant to gentamicin. Race was the only factor associated with early bacteremia (hazard ratio 2.3 for non-Caucasian, non-African-American patients, CI 1.3,4.3, P,=,0.007) Conclusions Early bacteremia is common after HSCT, despite the use of GD. Resistant Gram-positive organisms predominate, consistent with recent trends in immunocompromised patients. Although used in practice, there is no clear evidence for the efficacy of GD and this study provides the basis upon which to develop a randomized clinical trial evaluating the current GD regimen with placebo. © 2004 Wiley-Liss, Inc. [source] Treatment of CML in pediatric patients: Should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?PEDIATRIC BLOOD & CANCER, Issue 5 2004Michael A. Pulsipher MD Abstract Background Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Results Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Conclusions Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes. © 2004 Wiley-Liss, Inc. [source] Acute weight gain and diastolic dysfunction as a potent risk complex for post stem cell transplant atrial fibrillation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Kaniz Fatema The management of atrial fibrillation (AF) following stem cell transplant (SCTX) is often challenging because of the universal presence of profound bone marrow suppression. The incidence of and risk factors for AF/flutter following SCTX are not well known. A total of 395 multiple myeloma (MM) patients consecutively underwent SCTX between 2002 and 2005 at the Mayo Clinic, and 383 of whom, mean age 57 ± 9 years, had no history of evidence of AF/flutter constituted the study population. During 1,002 person-years of follow up, 39 (10%) patients developed first AF/flutter (incidence of 39 per 1,000 person years), and 28 of these (72%) occurred within 21 days of SCTX. In multivariable-adjusted analyses, weight gain of ,7% in the 1st week post-SCTX (HR 3.68; P = 0.0120) and presence of diastolic dysfunction at MM diagnosis (HR 2.294; P = 0.0082) were independent predictors of AF/flutter. The risk of AF/flutter post-SCTX increased by about ninefold when both factors were present. Compared to age and sex-matched MM patients without SCTX, the risk of AF/flutter differed significantly only over the 1st year after MM diagnosis, during which SCTX was performed for the majority. Beyond the 1st year, there was no significant difference in risk of AF/flutter between the two groups. The data suggested that SCTX was associated with significantly increased risk of first AF/flutter, which typically occurred within the first 21 days of the transplant. Weight gain of ,7% was strongly predictive of first AF/flutter, and the risk was augmented by the presence of diastolic dysfunction at baseline. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||