Disturbance of haemostasis and
bleeding are rather frequent complications of
AL amyloidosis. These are frequently caused by increased fragility of capillaries, thrombocyte function disorders and coagulation cascade defects. The most frequent coagulation disorder is decreased
factor X activity. We describe a 34-year old female after
hysterectomy for myomatous uterus and metrorhagia. Before the surgery, the attending physicians did not identify any pathological changes suggesting a need for further investigations or presence of
AL amyloidosis. Post-surgery development was complicated by life-threatening diffuse haemorrhage. Extended investigations of coagulation cascade revealed reduction of
factor X activity to 16%. Targeted histological examination of the resected uterus confirmed AL
amyloid deposits consisting of kappa chains. The patient's bone marrow contained certain small level of multiplied kappa chains-expressing plasma cells (< 10%); monoclonal
immunoglobulins IgG K and free kappa chains were identified in serum. At that time, the patient did not satisfy the then valid Durie-Salmon criteria for
multiple myeloma and thus the patient was diagnosed with primary systemic
AL amyloidosis. The patient's condition gradually improved following substitution
therapy (Prothromplex, fresh frozen plasma and
erythrocyte transfusion) and
bleeding slowly ceased so that
chemotherapy with VAD (
vincristine,
adriamycin and
dexamethasone) was initiated 6 weeks after the surgery. A total of 8
chemotherapy cycles were administered and complete haematological remission was achieved after the 5th cycle. Administration of the 8 VAD
chemotherapy cycles resulted in increased
factor X activity;
bleeding complications subsided completely, thereby decreasing the risk of life-threatening
mucositis-associated haemorrhage. Consequently, tandem high-dose
chemotherapy (
melphalan 100 mg/m2) with autologous haematopoietic stem cells
transplantation was added to the treatment plan. Treatment was completed at the beginning of 2003 and, from that time, the patient is on continuous maintenance
therapy with
interferon alpha. Seven years from the diagnosis and 6 years from the completion of treatment the patient is in complete haematological remission, with no signs of organic damage caused by AL
amyloid and with normal
factor X activity.
Factor X activity increased at the time when complete haematological remission was achieved after 8 cycles of VAD
chemotherapy to 42%, it reached 68% the second year following high-dose
chemotherapy, 77% after 5 years and 85% after 7 years. We had considered administration of high-dose
chemotherapy in the standard regimen, i.e. following 4 cycles of VAD
chemotherapy, as too high risk in the described young female patient. Therefore, we administered 8 cycles of conventional
chemotherapy and only after complete haematological remission and partial organ response (
factor X activity increased to 42%) were achieved, we added tandem high-dose
chemotherapy to the treatment. We thus achieved long-term (7-years so far) complete haematological and organ remission. Increase in
factor X activity is explicit over the entire 7-year observational period. We recommend starting treatment of high-risk transplant patients with
AL amyloidosis with traditional
chemotherapy regimen and, in case of positive haematological and organ treatment response, we recommend re-examination of potential benefits and risks of high-dose
chemotherapy with
autologous transplantation.