Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy.

Oral acyclovir has been demonstrated to prevent reactivation of herpes simplex virus (HSV) infections when administered prophylactically to autologous bone marrow transplant (BMT) recipients or patients undergoing stem cell rescue therapy. Oral valacyclovir, which is converted in the body to acyclovir, has greater oral bioavailability than oral acyclovir and compared with oral acyclovir yields similar acyclovir plasma concentrations with less frequent (twice-daily) dosing. This study compared the efficacy of oral valacyclovir with that of oral acyclovir at preventing HSV mucositis in BMT recipients. A total of 60 HSV-1-positive patients scheduled for BMT or stem cell rescue therapy were treated prophylactically with valacyclovir 500 mg twice daily until resolution of neutropenia. Data from these patients were compared with those of a historical control group of 60 patients who had received acyclovir 600 mg every 6 h until resolution of neutropenia or acyclovir 125 mg/m(2) intravenously every 6 h. The results show that none of the patients developed oral or oropharyngeal HSV infection while receiving either treatment. Of the 60 patients receiving valacyclovir, 38 (63%) completed treatment without the need for intravenous acyclovir compared with 12 of 60 (20%) patients in the acyclovir group. Additionally, the total number of doses of drug administered to the valacyclovir group was significantly less than the number received by patients in the acyclovir group. No serious adverse events occurred in either group of patients. This study demonstrates that oral valacyclovir and acyclovir are comparably effective and safe in preventing reactivation of HSV infections in autologous BMT and stem cell recipients. The less frequent dosing schedule with valacyclovir compared with acyclovir offers a potential advantage for patients undergoing BMT who frequently suffer with severe mucositis and have difficulty taking oral medications.

Drug-induced thrombocytopenia presenting with isolated oral lesions: report of two cases.

Patients with platelet-mediated bleeding disorders often present with clinical manifestations of bruising and bleeding. Although these changes are detected most frequently on the skin and in the oral cavity, the nasal and genital mucosa, as well as the renal and gastrointestinal systems, also may exhibit signs of bleeding. In this report, we describe two patients who presented with isolated oral features: one with oral hemorrhagic bullae and a second with oral petechiae and gingival bleeding indicative of a bleeding disorder. Results of laboratory tests revealed severe thrombocytopenia and a careful history disclosed drug hypersensitivity as the cause. It is important to recognize the oral manifestations of thrombocytopenia since the oral cavity is a frequent site of hemorrhage and may be the only manifestation of the disease. Proper identification permits the prompt institution of treatment and prevention of serious complications.

Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hepatic complications are a major cause of illness and death after bone marrow transplantation. OBJECTIVE: To confirm the results of a pilot study that indicated that ursodiol prophylaxis could reduce the incidence of veno-occlusive disease of the liver. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Tertiary care teaching hospital. PATIENTS: 67 consecutive patients undergoing transplantation with allogeneic bone marrow (donated by a relative) in whom busulfan plus cyclophosphamide was used as the preparative regimen and cyclosporine plus methotrexate was used to prevent graft-versus-host disease. INTERVENTION: Before the preparative regimen was started, patients were randomly assigned to receive ursodiol, 300 mg twice daily (or 300 mg in the morning and 600 mg in the evening if body weight was > 90 kg), or placebo. MEASUREMENTS: Patients were prospectively evaluated for the clinical diagnosis of veno-occlusive disease, the occurrence of acute graft-versus-host disease, and survival. RESULTS: The incidence of veno-occlusive disease was 40% (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol recipients (P = 0.03). Assignment to placebo was the only pretransplantation characteristic that predicted the development of veno-occlusive disease. The most significant predictor of 100-day mortality was the diagnosis of veno-occlusive disease. The difference in actuarial risk for hematologic relapse in patients with chronic myelogenous leukemia and nonhepatic toxicities between the two groups was not statistically significant (13% in the ursodiol group and 20% in the placebo group; P > 0.2). CONCLUSION: Ursodiol prophylaxis seemed to decrease the incidence of hepatic complications after allogeneic bone marrow transplantation in patients who received a preparative regimen with busulfan plus cyclophosphamide.

Oral cavity complications of bone marrow transplantation.

Bone marrow transplantation, once regarded as experimental, has evolved into a standard treatment for a variety of malignancies. Considerable advances have been made in histocompatibility typing, pretransplantation chemotherapy, and posttransplantation immunosuppressive therapy as well as prophylaxis and treatment of infections. Oral complications develop in almost all patients, and their early recognition may result in the institution of prompt treatment and prolonged survival. Mucositis, often severe and extremely painful, develops in more than three quarters of bone marrow transplant recipients, and its prevention, unfortunately, remains unsatisfactory. Herpes simplex virus and Candida albicans account for most oral infections, although their incidence has been dramatically reduced by the institution of prophylactic agents. Graft versus host disease continues to be a significant complication of marrow transplantation, and the detection of commonly occurring oral changes may support its diagnosis.

Abciximab-associated profound thrombocytopenia: therapy with immunoglobulin and platelet transfusion.

First-time abciximab administration was associated with acute profound thrombocytopenia in 4 of 575 consecutive patients. Therapy with platelet transfusion, but not intravenous immunoglobulin, was associated with a rapid and sustained increment in circulating platelet count and clinical hemostasis.

Comparison of thromboelastography to bleeding time and standard coagulation tests in patients after cardiopulmonary bypass.

This prospective study of 36 adult patients undergoing cardiopulmonary bypass (CPB) was conducted to determine the utility of thromboelastography (TEG) versus platelet studies (bleeding time, platelet count, mean platelet volume) and standard coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen) to more effectively discriminate patients likely to benefit from platelet or fresh frozen plasma (FFP) transfusion. Although the sensitivities of the bleeding time (71.4%) and platelet count (100%) were similar to the TEG (71.4%), the specificity (89.3%) of the TEG was greater than that of the bleeding time (78.5%) and platelet count (53.6%). Seven patients experienced clinically significant hemorrhage; 5 (71.4%) had an abnormal TEG. Three of 8 (38%) other patients with an abnormal TEG had no abnormal bleeding. Only 2 of 27 (7.4%) patients with a normal TEG had abnormal bleeding requiring platelet or FFP transfusion. Therefore, it is suggested that post-CPB patients with a normal TEG should not receive platelet or FFP transfusions empirically. If excessive bleeding is noted in a patient with a normal TEG, this suggests a surgically correctable etiology. Data from this series suggest that patients displaying an abnormal TEG appear to be at increased risk for hemorrhage; therefore, appropriate blood product support should be initiated at the first sign of accelerated bleeding.

Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients.

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.

Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide.

The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis.

Diversity of organ site involvement among malignant lymphomas of mucosa-associated tissues.

Fifteen cases of low-grade B-cell lymphoma involving unusual extranodal sites have been studied in comparison to cases reported or observed arising in typical mucosa-associated lymphoid tissues. In every case, histopathologic features conformed to those characteristic for lymphomas of mucosa-associated lymphoid tissues, including the production of lymphoepithelial complexes. Immunoglobulin light chain restriction was demonstrated by immunocytochemistry in 14 cases. Sites of involvement included the breast (6), skin (5), kidney (1), prostate (1), gallbladder (1), and uterine cervix (1). In three cases there was simultaneous or previous lymphoma of mucosa-associated lymphoid tissues identified in a more common mucosal site. It is concluded that the unifying concept of lymphomas of mucosa-associated lymphoid tissues applies to extranodal organs less commonly associated with mucosa-associated lymphoid tissues, as well as to those mucosal organ sites described in earlier series.