Incidence and Impact of Light Chain Associated (AL) Amyloidosis on the Prognosis of Patients with Multiple Myeloma Treated with Autologous Transplantation

Abstract

Little is known about the incidence of clinically occult AL amyloid in patients with multiple myeloma and its impact on prognosis of these patients. To address these issues, subcutaneous fat pad aspirates (SAFA) and bone marrow biopsies were evaluated for the presence of amyloid in a cohort of newly diagnosed patients with multiple myeloma prior to enrollment on a phase II study including tandem transplants. Organ directed biopsies were performed when clinically indicated. Presence of amyloid at > or = 1 site was noted in 32 patients (38%). SAFA was positive in 25 (31%), bone marrow in 8 patients (10%) and other organ sites in 7 patients. Patients with and without amyloid did not differ in disease characteristics, in particular no lambda predominance was observed in patients with amyloid. Event free survival (59+ vs 52 months; p = .9) and overall survival (59+ vs 66+ months; p = .9) were similar in both groups. Even the seven patients with symptomatic organ involvement with AL amyloid had a median overall survival of 38+ months. In conclusion, AL amyloidosis occurs more often than previously reported, but its presence does not influence the outcome of these patients after transplantation.

Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature

“…Some authors found out MM-associated asymp-amyloid in up to 26% of patients at the time of diagnosis (8); this was also an independent high-risk prognostic factor for MM patients, thus suggesting need for searching amyloid and need for aggressive treatment. Others believe that AL deposits, even if not rare, are clinically inconsequential and should not influence MM therapy, so active screening is unnecessary (6,9).…”

“…Table 3 puts our findings into the context of prior reports. One of the first reports addressing this question was by Desikan et al (6), who prospectively evaluated fat pad aspirate and BM biopsy for amyloid deposit in a cohort of 84 MM patients. Amyloid was detected in 38% of patients; fat pad aspirate was positive in 25% and BM in 10% of cases and other organ sites in 7 patients.…”

“…di Ematologia con trapianto, Azienda Ospedaliera Universitaria Policlinico di 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 (5,6,7,8) and in up to 15% of all MM patients a clinically overt AL appear during the course of index MM (3,5)). …”

Clinical Features and Treatment Response of Light Chain (AL) Amyloidosis Diagnosed in Patients With Previous Diagnosis of Multiple Myeloma

“…Some reports suggest that 10% to 15% of patients with MM may develop overt AL amyloidosis during the course of their disease, and up to 38% of patients with MM may have clinically occult AL amyloid deposits. 3,4 We designed the current study to iden tify and describe the clinical features, diagnosis, treatment patterns and response, and outcome among patients who were diagnosed as having AL amyloidosis subsequent to a diagnosis of MM. We describe 47 patients with a histologic diagnosis of AL amyloidosis, made at least 6 months after the initial diagnosis of MM, thus excluding patients with symp tomatic AL amyloidosis at the time of the diagnosis of MM.…”

“…A carpal tunnel tissue biopsy was positive in 6 patients (13%), and 1 patient had a positive biopsy from a gluteal mass. The diagnosis of AL amyloidosis was established by demonstrating amyloid in various target organs in 12 patients (26%) (lung [5], kidney [4], heart [1], small bowel [1], and liver [1]). Echocardiographic findings suggestive of amyloid cardiomyopathy, such as thick ened ventricular wall and/or interventricular septum, and diastolic dysfunction were observed in 15 patients (32%); corresponding restrictive changes were revealed by cardiac catheterization in 1 patient.…”