Search

Background: Hemorrhagic complications are frequently implicated clinically for the high morbidity and mortality of acute graft versus host disease (GVHD), however, only few reports characterize the incidence and timing of bleeding in relation to GVHD, and essentially no study has quantified the effect of bleeding on survival of allogeneic patients with GVHD. This study examines the association of bleeding with acute GVHD and the effect of both complications on survival., Methods: A total of 463 allogeneic patients transplanted at the Johns Hopkins Hospital, were included in the study. Bleeding evaluation was based on daily scores of intensity and blood transfusions. All bleeding sites were recorded. GVHD staging was defined by the extent of rash, serum bilirubin, diarrhea, and confirmatory histology., Results: The incidence of GVHD was 27.4%, bleeding occurred in 40.2%. The incidence of bleeding was higher in patients with GVHD as compared with non-GVHD, and correlated with GVHD severity. The higher bleeding incidence in GVHD was due to gastrointestinal hemorrhage, hemorrhagic cystitis, and pulmonary hemorrhage. While the majority of bleeding (51/75) in non-GVHD patients initiated within 30 days after bone marrow transplantation (BMT), only 32.3% (21/65) of the bleeding in the GVHD group initiated within 30 days, and the risk for bleeding continued until day 100. Bleeding was a late event compared to GVHD, however, most bleeding episodes were associated with active GVHD. Both GVHD and bleeding were individually associated with reduced survival, with profound additive adverse effect: median survival in 221 nonbleeding non-GVHD was >83.2 months, GVHD nonbleeding (39 patients) had median of 10.6 months, bleeding non-GVHD (99 patients) had median of 4.3 months, and median survival of the GVHD bleeding group (85 patients) was 3.2 months., Conclusions: Our results support an association of bleeding with acute GVHD, suggesting that GVHD is a risk factor for bleeding after BMT. The occurrence of bleeding clearly identified poor outcome subgroup within GVHD, suggesting further evaluation for clinical application of bleeding in the assessment of GVHD severity.

Chronic graft-versus-host disease (GVHD) is the most common late complication of allogeneic bone marrow transplantation (BMT). The sclerodermatous form of the disease is often refractory to standard treatment modalities. Based on reports of response to etretinate, a synthetic retinoid, among patients with scleroderma, we have added etretinate to the treatment regimen of 32 patients with refractory sclerodermatous chronic GVHD. This case series is comprised mainly of patients who had chronic GVHD of long duration (median of 30 months before the initiation of etretinate). Most had failed to respond to three or more agents before etretinate treatment was started. Clinical response was assessed after 3 months of therapy. Five patients did not complete a 3-month trial. Among the 27 patients evaluable for response, 20 showed improvement including softening of the skin, flattening of cutaneous lesions, increased range of motion, and improved performance status. Four showed no response after 3 months of therapy and 3 had progression of their sclerosis. Overall, etretinate has been fairly well tolerated in our patients, with skin breakdown and/or ulceration leading to its discontinuation in 6 patients. We believe the results in our patients are encouraging and suggest that further evaluation of etretinate in the treatment of sclerodermatous chronic GVHD is warranted.

Chronic graft-versus-host disease (GVHD) remains a difficult clinical problem to treat and manage. We have reviewed our treatment of 40 patients treated at a single institution with PUVA (ultraviolet irradiation and psoralen) over a 14 year period. Thirty-five patients were treated for refractory chronic GVHD and five patients were treated at presentation of high-risk chronic GVHD. Overall, 31 of 40 patients improved on PUVA treatment. Sixteen patients achieved a complete response to PUVA added to their GVHD regimen. Four of the 15 partial responders had complete resolution of cutaneous GVHD but persistence of other systemic manifestations. The remaining partial responders had at least a 50% improvement in GVHD. We have also used PUVA with a glass fiber extension to treat intra-oral GVHD. PUVA is well tolerated with a high rate of response in the skin and mild side effects except for three patients who had therapy discontinued after phototoxicity (burn).

Background: Allogeneic graft-versus-host disease is associated with decreased rates of tumor relapse. The addition of interferon gamma to cyclosporine, given to induce graft-versus-host disease after autologous bone marrow transplantation, increases the extent of the cutaneous eruption., Objective: Our purpose was to describe the clinical and histologic cutaneous changes in 10 patients with breast cancer who received interferon gamma to potentiate graft-versus-host disease after autologous bone marrow transplantation modified by cyclosporine., Methods: Ten women receiving autologous bone marrow transplantation modified by the administration of cyclosporine and interferon gamma were observed clinically with sequential biopsy of the skin weekly and at the time of cutaneous eruptions., Results: Erythroderma (stage 3) developed in five women after the first or second administration of interferon gamma. At least on skin biopsy specimen from 7 of the 10 women showed grade 2 changes of graft-versus-host reaction, including all patients with erythroderma. Epidermal intercellular edema was prominent in these specimens with expression of keratinocyte HLA-DR and intercellular adhesion molecule 1. Induction of keratinocyte HLA-DR and intercellular adhesion molecule 1 expression was not observed in specimens from normal skin during administration of interferon gamma., Conclusion: This protocol causes a more widely distributed cutaneous eruption, including erythroderma (50%), than autologous bone marrow transplantation and cyclosporine administration alone (3%). Whether it will affect survival is unknown.

Background: Graft-vs-host disease (GVHD) represents one of the major complications of allogeneic bone marrow transplantation (BMT) but is less common in autologous BMT. Following autologous BMT, chronic GVHD has been reported in only four patients, all of whom had a self-limited sclerodermoid form. Lichenoid chronic GVHD has not been previously reported in an autologous BMT patient., Observations: Mucosal and cutaneous lichenoid lesions and histologic findings compatible with chronic lichenoid GVHD developed in a patient 35 days after autologous BMT was performed. The onset of clinical lesions at 35 days after BMT is not incongruent with the diagnosis of chronic lichenoid GVHD (rather than a graft-vs-host reaction) and may have been augmented by cyclosporin A in a manner similar to animal model experiments., Conclusion: All forms of GVHD can and do occur following autologous BMT.

Background: Chronic graft-vs-host disease (GVHD) is a late complication of allogeneic bone marrow transplantation and is associated with high morbidity and mortality. While the pathogenesis of chronic GVHD is not fully understood, several observations and studies suggest that viral infections may play a role. We describe two patients who developed linear lichenoid chronic GVHD. The dermatomal distribution of their lesions suggests an association with herpes zoster virus infection., Observations: Two allogeneic bone marrow transplantation patients developed violaceous papules in a dermatomal distribution. Histologic examination of these lesions revealed dyskeratosis, vacuolar changes in the basal layer, and a mild perivascular and interstitial infiltrate, diagnostic of lichenoid chronic GVHD., Conclusions: The linear distribution of our patients' lichenoid chronic GVHD is unique and may represent an association with herpes zoster virus infection, providing further support for a role for viral infections in the pathogenesis of chronic GVHD.

The purpose of this study was to describe the incidence, onset, duration, severity, and other relevant characteristics of mucositis and pain in patients undergoing bone marrow transplant (BMT) who were receiving high-dose chemotherapy (cytoxan, busulfan, and etoposide) without total body irradiation. A descriptive, longitudinal design was used to study a sequential sample of 47 patients undergoing allogeneic and autologous BMT. Each day, from 9 days prior to BMT through 21 days after BMT, nine anatomic regions of patients' mouths were assessed for extent and severity of mucositis. Oral pain was measured using the Short-Form McGill Pain Questionnaire. Forty-two patients (89%) developed mucositis, which, on average, began 3 days after transplant, lasted 9.5 days, and resolved by 12.6 days post-transplant. Thirty-six patients (86%) reported pain that began, on average, 4.5 days after transplant, lasted 6.5 days, and resolved by 11 days post-transplant. During the initial weeks following BMT, systematic assessment of the oral cavity areas that are at high risk for mucositis should assist nurses in detecting early oral complications and in initiating specific interventions. Additionally, attention needs to be given to the assessment and management of mucositis-related oral pain. Future nursing research should be conducted to examine efficient clinical methods of assessing mucositis and oral pain and to test prophylactic and therapeutic interventions.