pulmicort and Hematologic-Neoplasms

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Budesonide; Calcineurin; Calcineurin Inhibitors; Child; Child, Preschool; Cord Blood Stem Cell Transplantation; Enzyme Inhibitors; Female; Gastrointestinal Tract; Graft vs Host Disease; Hematologic Neoplasms; Histocompatibility Testing; HLA Antigens; Humans; Infant; Male; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Severity of Illness Index; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome

Budesonide (BUD) is a steroid with a low bioavailability, which has been used for the treatment of oral manifestations of chronic GVHD (cGVHD). We retrospectively evaluated the efficacy of BUD in the treatment of gastrointestinal cGVHD. Thirteen patients (median age 47 years) receiving BUD for the treatment of cGVHD after allogeneic hematopoietic SCT for hematological malignancies were evaluated for response. Five patients had isolated gastrointestinal cGVHD and 8 patients had mild multiorgan involvement including gastrointestinal manifestations. Six patients received CYA at the time of onset of cGVHD, which was continued during treatment with BUD. Treatment consisted of BUD, with an initial daily dose of 3 x 3 mg orally. Complete resolution of cGVHD was achieved in seven patients, and one patient achieved partial remission of cGVHD. One patient achieved complete resolution of gastrointestinal cGVHD, while systemic manifestations of cGVHD remained stable. Four patients progressed on BUD. Owing to the predominantly local effect, relapse of symptoms of cGVHD after withdrawal of immunosuppression (n=3) as well as progression of GVHD at other sites (n=3) has been observed. BUD represents a treatment option in mild-to-moderate cGVHD, which is well tolerated and associated with a high response rate in gastrointestinal cGVHD.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Cyclosporine; Female; Gastrointestinal Diseases; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Remission Induction; Transplantation, Homologous

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.

Topics: Adult; Budesonide; Candidiasis, Oral; Chronic Disease; Cohort Studies; Cyclosporine; Drug Evaluation; Drug Therapy, Combination; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Male; Middle Aged; Mouthwashes; Pain Measurement; Peripheral Blood Stem Cell Transplantation; Prednisone; Retrospective Studies; Sodium Chloride; Stomatitis; Transplantation Conditioning; Treatment Outcome

Bronchiolitis obliterans (BO) is a potentially life-threatening complication following allogeneic stem cell transplantation (SCT) and usually carries a poor prognosis. Immunosuppressive medications are the main treatment, but are rarely effective, especially when the disease is severe. Thus, both early detection and alternative therapeutic approaches of post SCT BO are needed. We report our experience with Budesonide/Formoterol, an inhaled steroid and long-acting bronchodilatator combination, in a group of patients with mild to moderately severe BO after SCT whose systemic immunosuppressive treatment had not been modified. Thirteen patients were treated. The diagnosis of BO was based on the presence of respiratory symptoms and air-trapping on expiratory lung high-resolution computed tomography in all patients, associated with irreversible airflow obstruction in seven cases. The median follow-up was 12.8 months (range: 5-29 months). All patients improved clinically, and both forced expiratory volume in 1 (FEV(1)) and mean expiratory flow values increased significantly during follow-up (534+/-268 ml in absolute values and 36+/-27% compared to pretreatment values for FEV(1); P<0.02). These encouraging results provide new insights in the therapeutic approach of BO after SCT and require confirmation in a larger group of patients with a longer follow-up.

Topics: Administration, Inhalation; Adolescent; Adult; Bronchiolitis Obliterans; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Follow-Up Studies; Formoterol Fumarate; Glucocorticoids; Hematologic Neoplasms; Humans; Male; Middle Aged; Prognosis; Radiography; Stem Cell Transplantation; Transplantation, Homologous