Francesca Saltarelli

Absolute lymphocyte count is a prognostic factor in diffuse large B-cell lymphoma

imab is associated with a reduction in IgG antibodies to ADAMTS13. British Journal of Haematology, 136, 451–461. Yarranton, H., Lawrie, A.S., MacKie, I.J., Pinkoski, L., Corash, L. & Machin, S.J. (2005) Coagulation factor levels in cryosupernatant prepared from plasma treated with amotosalen hydrochloride (S-59) and ultraviolet A light. Transfusion, 45, 1453–1458.

Quick response to bortezomib plus dexamethasone in a patient with AL amyloidosis in first relapse.

High-dose melphalan followed by autologous stem cell transplantation is currently the treatment of choice in fit patients affected by AL amyloidosis. However, the majority of AL amyloidosis patients is ineligible for transplant or experience relapse after this kind of treatment. A new treatment approach is represented by bortezomib, a proteasome inhibitor widely used in multiple myeloma. We used a combination therapy of bortezomib and dexamethasone in a 66-years-old woman affected by systemic AL amyloidosis and relapsed after nine courses of oral melphalan and dexamethasone. The patient received only two courses of bortezomib and dexamethasone due to severe somatosensory polyneuropathy development. Anyway complete remission (CR) and organ response were both achieved after 1.5 and 2.5 months, respectively. Disease relapse occurred after 7 months of a CR period. The excellent response obtained with bortezomib and dexamethasone in a pretreated and relapsed patient represents a new chance of treatment in AL amyloidosis even though it is complicated by multiorgan impairment. Introduction: Primary systemic AL amyloidosis is clinically characterized by progressive dysfunction of multiple visceral organs, including heart, kidneys, liver, and gastrointestinal (GI) tract, and it is pathologically caused by amyloid deposition in various tissues due to the presence of an underlying plasma cell dyscrasia in the bone marrow [1,2]. Prognosis is poor, particularly in patients with cardiac involvement [3,4]. Prompt initiation of treatment is required in systemic form in order to inhibit the growth of malignant clone and to reduce the supply of the amyloidogenic light chains. Treatment choice depends on patient’s age and performance status like on the type and extent of organ damage. The therapeutic armamentarium has greatly expanded in recent years from melphalan–prednisone as single resource in 1977 to several effective therapies including highdose dexamethasone-based regimens combined with melphalan (MDex), thalidomide (ThalDex), and cyclophosphamide-thalidomide (CTDex), high-dose melphalan followed by autologous stem cell transplantation (SCT), to the new agents basically represented by lenalidomide and bortezomib [5]. Bortezomib is a small boronic acid derivative that inhibits the 26S proteosome which can produce clinically useful remissions in patients with relapsed myeloma [6,7]. Bortezomib has efficacy in myeloma refractory to thalidomide [8] but has substantial, although often manageable, toxicity [9]. Encouraging data from myeloma suggested that it might also be a useful agent in AL amyloidosis. Kastritis et al. reported for the first time the efficacy of the proteasome inhibitor in patients with AL amyloidosis. The hematologic response rate was observed in 94%, including a 44% CR. The median follow-up was 11.2 months [10]. Wechalekar et al. conducted a trial in which heavily pretreated patients received bortezomib with or without dexamethasone. Bortezomib was median the third-line therapy (range 1–6). Seven out of nine (77%) patients who were given the combination of Btz/Dex responded. The median survival was not reached at 24 months from the end of treatment [11]. Lamm et al. reported a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis. Eighteen patients (69%) received Btz/Dex as first-line treatment. The overall response rate was 54%, with eight patients achieving a hematologic complete remission. All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in three patients (12%). Toxicities were manageable, with hematological side effects being most common [12]. Methods: Between September and October 2007, at Clinical Haematology Department – Sant’Andrea Hospital in Rome, we treated a 66-years-old woman with relapsed systemic AL amyloidosis with two courses of a combination therapy based on bortezomib (1.3 mg/m day 1, 4, 8, 11 q21) plus dexamethasone (20 mg p.o. day 1–2, 8–9 q21). Before bortezomib plus dexamethasone, the patient had been treated with 9 courses of oral melphalan (0.18 mg/kg day 1–4 q28) and dexamethasone (40 mg p.o. day 1–4 q28) as first-line treatment and disease relapse occurred after a 19 months’ complete remission period (Table 1). During treatment, patient received anti-infective prophylaxis with cyprofloxacine 250 mg b.i.d from day 1 to day 9 of every cycle and with acyclovir 200 mg b.i.d continuously for HVZ virus reactivation. Baseline evaluation included serum and urine immunofixation and electrophoresis, liver and renal function assessment, ECG, cardiac and abdominal ultrasonography, (Figure 1) and bone marrow aspirate. Plasmatic NT-proBNP and troponine I were used for heart disease assessment and response to treatment. Full blood count, biochemical survey, and serum free light chains (sFLC) were assessed before and after the end of treatment. 152