Treatment of AL‑ amyloidosis – results from one clinic and review of published experience with new agents (bortezomib, thalidomide and lenalidomide) in AL‑ amyloidosis
Authors:
Z. Adam 1; L. Pour 1; M. Krejčí 1; L. Zahradová 1; A. Křivanová 1; J. Šmardová 3; L. Kovářová 1; S. Štěpánková 2; M. Moulis 3; L. Křen 3; K. Veselý 4; I. Svobodová 4; Z. Čermáková 5; M. Nedbálková 6; J. Mayer 1; R. Hájek 1
Authors‘ workplace:
Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jiří Vorlíček, CSc. 2Interní hepatogastroenterologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jan Lata
1
Published in:
Vnitř Lék 2010; 56(3): 190-209
Category:
Original Contributions
Overview
Patients:
Fifteen patients with light chain deposits in the form of AL‑ amyloidosis and 2 patients with light chain deposition as amorphous matter (light chain deposition disease) were treated at our clinic as of 1999. Median age at the diagnosis was 63 (34– 77) years. The light chain deposition caused: nephrotic syndrome in 12 (70%) patients, renal insufficiency with reduced filtration in 4 (23%) patients, cardiomyopathy in 4 (23%) patients, hepatosplenomegaly in 2 (12%) patients, manifest coagulopathy in 2 (12%) patients, periorbital hematoma in 2 (12%) patients, visceral and somatic neuropathy in 2 (12%) patients. Treatment with high‑dose dexamethasone in combination with adriamycin and vincristine (VAD) or cyclophosphamide (CAD or just CD) was used in 11 patients. In 4 patients, therapy was completed with high‑dose chemotherapy and autologous transplantation; complete haematological and organ treatment response was achieved in all 4 patients with remission lasting 113+, 87+, 50, 45+ months. Of the remaining 7 patients in whom high‑dose dexamethasone therapy was not completed with high‑dose chemotherapy, 3 achieved complete haematological remission (CR) and very good partial remission (VGPR), with 2 patients achieving complete organ treatment response. Organ response in the third patient cannot be assessed due to the short evaluation period. PR with no organ treatment response was achieved in other 2 patients and 2 patients died during the treatment. Therapy with prednisone and alkylating cytostatics was used in 2 patients with serious organ damage, both patients died after a short period of time due to the disease and thus treatment response cannot be evaluated. Combination of thalidomide, dexamethasone and cyclophosphamide (CTD) was used in 4 patients. Two of these patients did not complete full 2 cycles, one for unmanageable thalidomide‑associated constipation, the other died. Two patients underwent a total of 5 and 6 cycles of this treatment with PR effect and plateau after the previous decline of monoclonal immunoglobulin concentrations. Treatment combination of bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) was used in three patients. In one patient (6 completed CTD cycles with the PR result) this combination led to complete haematological remission, complete remission was also achieved in the second patient and the application of 2 CVD cycles led to CR in the third (5 CTD cycles with PR result). Just one of the 3 female patients has been followed up for more than 12 months and so it is possible to evaluate organ treatment response in this patient; nephrotic syndrome ceased, meaning that organ CR has been achieved.
Conclusion:
Early diagnosis (before severe organ damage occurs) enables administration of aggressive treatment (high‑dose chemotherapy and autologous transplantation) with the outlook of complete haematological and organ treatment response. New drugs thalidomide and bortezomib further expand treatment armamentarium; according to our limited experience and published information, bortezomib may be considered as very effective and well tolerated agent suitable, in combination, for patients with the diagnosis of AL‑ amyloidosis.
Key words:
AL‑ amyloidosis – light chain deposition disease – monoclonal gammopathy – thalidomide – bortezomib – high‑dose chemotherapy and autologous transplantation – nephrotic syndrome – cardiomyopathy – neuropathy – coagulopathy
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