Improving security of autologous hematopoietic stem cell transplant in patients with light-chain amyloidosis

Abstract

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

Treatment of AL Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement 2020 Update

“…In the 4 largest modern series on ASCT in AL amyloidosis (with or without induction), HR was achieved in 83% to 94% of patients, hematologic CR in 43% to 56%, and OR in 56% to 69%, and median OS was 6.3 to 10.9 years. 6,[91][92][93] The actuarial 15-year survival rate in our center among patients undergoing ASCT is 30%, 8 a figure that is expected to be higher with improvements in outcomes in recent years. 46 In a study focusing on AL patients surviving 10 years or more, those who underwent ASCT were less likely to require subsequent therapies compared with those receiving standard-intensity therapies.…”

Hidden in Heart Failure

“…[90] Patients with significant cardiac involvement are unable to tolerate the preferred treatment of high-dose chemotherapy with autologous stem cell transplantation, emphasising the importance of early diagnosis. [95] Mortality at 6 months remains high at 24%, but is improving as patients are diagnosed earlier with less severe cardiac involvement. [96]…”

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

“…The estimated incidence of ES ranged between 5% and 72% [30,31] depending on the diagnostic criteria implemented [21,22]. The onset of ES has been associated with ASCT for solid tumors (breast cancer), autoimmune diseases (multiple sclerosis) and monoclonal gammopathies (MM, AL amyloidosis and POEMS syndrome) that included the use of post-ASCT G-CSF, a high infused CD34 + cell dose, earlier and more rapid granulocyte recovery and the introduction of bortezomib and immunomodulatory drugs as induction therapy in MM [18,[23][24][25][26][32][33][34]. The most important aspect in managing ES is early recognition, ruling out alternative causes, and the use of corticosteroids (methylprednisolone 1 to 1.5 mg/Kg/day for two or three days) following a quick tapering regimen [26].…”