Risk-adapted Therapy for Primary Systemic (AL) Amyloidosis
Risk-adapted Therapy for Primary Systemic (AL) Amyloidosis
High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy
 for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been
 high. The investigators performed a phase II trial of risk-adapted SCT followed by adjuvant
 dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response
 rates. Patients with newly diagnosed AL involving £2 organ systems were assigned to MEL 100,
 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement. Patients
 with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant
 thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). TRM was 4.4%.
 Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment
 and 13 (42%) achieving an improvement in hematological response. By intention-to-treat,
 overall hematological response rate was 71% (36% complete response) with 44% having organ
 responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence
 interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/ dex is feasible and results in low
 TRM and high hematological and organ response rates in AL patients.
High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy
 for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been
 high. The investigators performed a phase II trial of risk-adapted SCT followed by adjuvant
 dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response
 rates. Patients (n=45) with newly diagnosed AL involving £2 organ systems were assigned to
 MEL 100, 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement.
 Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of
 adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy).
 Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system
 (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant
 therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement
 in hematological response. By intention-to-treat, overall hematological response rate was 71%
 (36% complete response) with 44% having organ responses. With a median follow-up of 31
 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with
 adjuvant thal/ dex is feasible and results in low TRM and high hematological and organ
 response rates in AL patients.(British Journal of Haematology 2007;139:224-33)