Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD compared with patients without cGVHD (P < .

Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study.

The most commonly used grading system for acute graft-versus-host disease (aGVHD) was introduced 30 years ago by Glucksberg; a revised system was developed by the International Bone Marrow Transplant Registry (IBMTR) in 1997. To prospectively compare the 2 classifications and to evaluate the effect of duration and severity of aGVHD on survival, we conducted a multicenter study of 607 patients receiving T-cell-replete allografts, scored weekly for aGVHD in 18 transplantation centers. Sixty-nine percent of donors were HLA-identical siblings and 28% were unrelated donors.

Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens.

Oral mucositis occurs in up to 75% of recipients of high-dose chemoradiotherapy conditioning regimens used for allogeneic hematopoietic stem cell transplantation (HSCT). As a result of mucositis, narcotic analgesia and total parenteral nutrition (TPN) are commonly required after HSCT. Methotrexate, an antiproliferative graft-versus-host disease (GVHD) prophylaxis agent, impairs mucosal regeneration and worsens and prolongs mucositis.

Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations.

New approaches for preventing and treating chronic graft-versus-host disease.

Despite improvements in the practice of allogeneic hematopoietic stem cell transplantation (HCT) over the last 25 years, chronic graft-versus-host disease (GVHD) remains a substantial problem with little change in the incidence, morbidity, and mortality of this complication. In fact, with increased use of peripheral blood, transplantation of older patients, and less immediate transplantation-related mortality, the prevalence of chronic GVHD may increase. One of the difficulties in combating chronic GVHD is a lack of understanding about the pathophysiology of the syndrome.

Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission.

Minor histocompatibility antigens (mHAs) are known targets of donor T cells after allogeneic hematopoietic stem cell transplantation (HSCT). In contrast, B-cell responses to mHAs have not been extensively characterized and the clinical significance of antibodies to mHAs is unknown. We tested 121 patients who underwent HSCT and 134 healthy donors for immunoglobulin G (IgG) antibodies against 5 mHAs encoded by genes on the Y chromosome (DBY, UTY, ZFY, RPS4Y, and EIF1AY).

Association of transplant center and physician factors on mortality after hematopoietic stem cell transplantation in the United States.

The effect of the organization and delivery of health care at medical centers, referred to as "center effects," with clinical outcomes after hematopoietic stem cell transplantation (HSCT) is not clear. We examined the association between center and treatment provider factors and mortality after HSCT. We surveyed 163 (87% response rate) United States transplantation centers that performed HLA-identical sibling HSCT for leukemia or autologous HSCT for lymphoma between 1998 and 2000 among patients at least 18 years old.

Catheter-related bloodstream infection caused by Mycobacterium brumae.

Mycobacterium brumae is a rapidly growing environmental mycobacterial species identified in 1993; so far, no infections by this organism have been reported. Here we present a catheter-related M. brumae bloodstream infection in a 54-year-old woman with breast cancer.

Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age.

Nonmyeloablative stem cell transplantation (NST) is increasingly used in older patients. The impact of the shift from myeloablative transplantation to NST on relapse, transplant complications, and outcome has yet to be fully examined. We performed a retrospective analysis of 152 patients older than 50 years undergoing NST or myeloablative transplantation.

Extended follow-up of patients treated with imatinib mesylate (gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease.

Purpose: Over the last several years, donor lymphocyte infusions have become the standard approach for patients with chronic myelogenous leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT). Recent reports indicate that imatinib mesylate (Gleevec) can induce remissions in these patients as well. Less is known about the extent and durability of these responses.

Sources of dietary iodine: bread, cows' milk, and infant formula in the Boston area.

Dietary iodine is essential for thyroid hormone production. Although U.S.

Patient-reported outcomes in multiple myeloma.

Multiple myeloma is an incurable malignancy of plasma cells. People with multiple myeloma may experience a variety of disease-related symptoms because of bony destruction, bone marrow infiltration, renal failure, immunodeficiency, and the psychosocial burden of a cancer diagnosis. Exciting new therapies and treatment approaches are becoming available but often bring unwanted side effects.

Physicians' attitudes about quality-of-life issues in hematopoietic stem cell transplantation.

Studies investigating quality of life (QOL) after hematopoietic stem cell transplantation demonstrate the spectrum of QOL outcomes awaiting survivors. Nevertheless, how transplantation physicians interpret and apply QOL information to clinical practice is poorly understood. We conducted a cross-sectional survey of transplantation physicians to address these issues and received 180 (24%) responses from physicians in 29 countries.

Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial.

The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted.

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 microg/kg intravenously on days 1 and 15; 18 received 9 microg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 microg/kg intravenously on days 1 to 5 and 15 to 19.

Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation.

Methotrexate in combination with a calcineurin inhibitor is a standard graft-versus-host disease (GVHD) prophylactic regimen in allogeneic stem cell transplantation. However, methotrexate is associated with delayed engraftment, mucositis, idiopathic pneumonia syndrome, and other transplant-related complications. Sirolimus, a novel immunosuppressant without methotrexate's toxicities, has been used successfully in solid organ transplantation.

A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome.

Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL).

Sulfadiazine-induced nephrolithiasis detected by spiral CT scan.

Nephrolithiasis is a known complication of the use of sulfadiazine in the treatment of cerebral toxoplasmosis. Radiographic diagnosis of this complication has historically been challenging. Between March 1999 and June 2002, 11 patients were treated for cerebral toxoplasmosis with sulfadiazine-containing therapy.

Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in the United States and Canada.

Purpose: Differences in survival among ethnic groups in the United States are reported in numerous diseases and treatment strategies. Whether survival after allogeneic hematopoietic stem-cell transplantation (HSCT) differs by ethnicity is uncertain.

Patients And Methods: Patients (n = 6443) receiving HLA-identical sibling HSCT for acute or chronic leukemia in the United States or Canada between 1985 and 1999 and reported to the International Bone Marrow Transplant Registry were included.

Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study.

Acute graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). It has been proposed that tumor necrosis factor alpha (TNF-alpha) blockade with infliximab may be an effective treatment for severe (grades III-IV) GVHD. We determined if infliximab use in this high-risk population was associated with an additional increased risk of non-Candida invasive fungal infections (IFIs).

A phase 2 study of bortezomib in relapsed, refractory myeloma.

Background: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity.

Methods: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.

Optimistic expectations and survival after hematopoietic stem cell transplantation.

An optimistic attitude is hypothesized to be beneficial when facing a life-threatening medical condition. However, the actual relationship of high expectations for treatment success and medical outcome is controversial. Using a prospective cohort of 313 autologous and allogeneic hematopoietic stem cell transplant patients enrolled July 1996 through November 1999, we tested whether patient-reported expectations before transplantation were associated with survival and quality of life following the procedure.