Allogeneic and Syngeneic Hematopoietic Cell Transplants in Patients with AL-Amyloidosis: A Report from the European Group for Blood and Marrow Transplantation (EBMT).

AL amyloidosis is caused by a plasma cell dyscrasia in which clonal immunoglobulin light chains deposited in tissues leads to organ failure and death. Treatment with high dose melphalan and autologous PBSC rescue produces hematologic remissions in approximately 40% of evaluable patients and improvements in organ disease and quality of life. For a subgroup of patients, an allogeneic hematopoietic cell transplantation (HCT) may be useful. There is little experience with this procedure in patients with AL amyloidosis. We report the patients (pts) who were registered within the EBMT database. Eleven pts (median age 45 years, range 30–63; 3 female) with AL amyloidosis (n=10) or with multiple myeloma plus AL amyloidosis (n=1) underwent allogeneic (n=8) or syngeneic ( n=3) HCT during 1987–2002, 7 of them before 2000. Donors of allogeneic transplants were matched related siblings. Main organ manifestations were kidney, heart and liver. Indications for allogeneic HCT were young age, relapse after autologous HCT (n=2) and progressive or refractory disease. Conditioning regimen was ablative in 4 pts and reduced-intensity conditioning (RIC) was used in the other 4 pts. Three pts had T cell depletion as graft-versus-host-disease (GvHD) prophylaxis. Engraftment was evaluable in 7/8 pts, 2 pts rejected their grafts and 5 pts had durable engraftment. One out of 5 evaluable pts developed acute GvHD (grade IV), and 1 of 3 evaluable pts developed chronic GvHD (limited disease). Five pts (62,5%) died at a median of 51 (range 25 – 83) days after HCT, all before day +100. From 4 of these 5 pts causes of death are known: 1 pt died of a cerebral aspergillosis (day +54) and 3 pts died of amyloidosis. Three pts remain alive (median observation 27 months, range 12–79) after HCT. Best hematological responses after HCT in surviving pts were immunofixation-negative CR in 1 pt (with cGvHD), PR in 1 pt and SD in the third pt. One of the 3 pts with syngeneic HCT is alive about 60 months after the procedure, the other 2 pts. died of TRM day +7 and +18, respectively. In summary, a very high day +100 mortality was observed. Main problem was cardiac failure due to amyloidosis in the very early phase after HCT. Half of the pts survived RIC and ablative conditioning, respectively. We conclude that a very restrictive patient selection is necessary to decrease mortality as it has been shown for high-dose chemotherapy with autologous HCT. Whether RIC plays an more important role for this patient group in the future remains to be defined.