High incidence of gastrointestinal tract bleeding after autologous stem cell transplant for primary systemic amyloidosis

Abstract

Summary:Peripheral blood stem cell transplants have been associated with better response rates than conventional chemotherapy in patients with primary systemic amyloidosis. A higher incidence of gastrointestinal (GI) tract bleeding has been observed among amyloidosis patients undergoing peripheral stem cell transplantation. We retrospectively reviewed the medical records of such patients to identify those who had GI tract bleeding in the post-transplant period. Forty-five patients were studied. Nine patients had GI tract bleeding in the posttransplant period. The median post-transplant duration to onset of bleeding was 9.5 days (range 1 to 48 days). Three patients had lower GI tract bleeding, two had upper GI tract bleeding, and four had both. Diffuse esophagitis and gastritis were the most common findings on endoscopy. There were no correlations among the age, platelet nadir, or CD34 count of the graft and the risk of bleeding. Women were more likely to have GI tract bleeding (P = 0.015), as were patients with slow platelet engraftment (P = 0.02). Patients with multiorgan involvement and those on hemodialysis appeared to be at a higher risk of GI tract bleeding. The mean posttransplant hospital stay for those with GI tract bleeding was 37 days compared with 14.5 days for those who did not have GI tract bleeding (P = 0.0047). Bone Marrow Transplantation (2001) 28, 381-385. Keywords: GI bleeding; high-dose chemotherapy; stem cell transplantation; systemic amyloidosis Primary systemic amyloidosis is a rare plasma cell proliferative disorder with an incidence of nearly eight per million per year. The prognosis for patients diagnosed with the disorder remains poor, with a median survival of only 13 months for those seen within 1 month of diagnosis.1 In those with congestive cardiac failure, the median survival is only 4 months, and only 5% survive more than 10 years. Currently available therapy has a minimal effect on the natural history of the disease and includes combination chemotherapy with melphalan and prednisone.2-4 Addition of other drugs, namely vincristine, BCNU, and cyclophosphamide to melphalan and prednisone (VBMCP), has not improved the results over melphalan and prednisone alone.

A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study

“…In AL, most patients are hematologically normal yet have significant organ dysfunction at the site of amyloid deposition: heart, liver, nerve, kidney, or lung. Patients may die of cardiac arrhythmias, 8 fatal pulmonary toxicity, 36 intractable cardiac failure, 7 gastrointestinal tract bleeding, 37 or precipitous renal failure, 15 which is rarely if ever seen in multiple myeloma. The decision to treat a patient with AL by transplantation must be undertaken with extreme caution, and ultimately a phase 3 trial to assess transplantation will be necessary, so the mistakes of transplantation for breast cancer are not repeated.…”

Primary (AL) Amyloidosis in Plasma Cell Disorders

“…Localized or diffusely spread amyloid involvement of the submucosa, the muscularis mucosa, and subserosa, as well as the vasculature of the gastrointestinal (GI) tract, is frequently observed [9,22]. It is usually asymptomatic or associated with nonspecific symptoms, such as anorexia, nausea, diarrhea, abdominal pain, weight loss, or malabsorption [22] and pseudo-obstruction [3].…”

“…Hypercalcemia, dehydration, infection, nonsteroidal anti-inflammatory agents, and radiographic contrast media may contribute to renal failure. In more than half of the patients, renal function may recover within the first few months [22]. However, 18% of patients with AL amyloidosis require dialysis, which is associated with a median survival time of <1 year [23].…”

“…It is usually asymptomatic or associated with nonspecific symptoms, such as anorexia, nausea, diarrhea, abdominal pain, weight loss, or malabsorption [22] and pseudo-obstruction [3]. Motor dysfunction of the bowel may result from extensive mucosal amyloid deposition but is more often attributable to autonomic dysfunction [4].…”

Nephrotic Syndrome Due to Primary AL Amyloidosis, Successfully Treated with VAD and Subsequent High-dose Melphalan Followed by Autologous Peripheral Blood Stem Cell Transplantation.

“…Several reports have shownthat the rate of complete remission in the production of Mprotein reached around 60% or more (12,17). This therapy is, of course, more risky than other chemotherapeutic regimens in patients with amyloidosis-induced dysfunction in multiple vital organs (18,19). Recently, it has been reported that the performance status and degree of cardiac involvement are important as potentially fatal risk factors after high-dose melphalan with auto-PBSCTin patients with AL amyloidosis (20).…”