High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic light-chain amyloidosis (AL) and a risk-adapted approach to MEL dosing minimizes transplant-related mortality (

BJH 2007; 139
). The depth and duration of hematologic response to treatment with SCT or conventional chemotherapy have been shown to correlate with overall survival (OS). Patients who do not achieve a complete hematologic response (CR) after SCT and are initially observed have a median OS of 24 months (
Leukemia Lymphoma 2000;37:245
). In an effort to improve the OS of those not achieving CR, and based partly on trials in multiple myeloma showing benefit, we have explored adding early adjuvant therapy (AT) to the treatment of AL patients with persistent clonal plasma cell disease post-SCT. We have enrolled patients on two consecutive SCT+AT protocols, the first utilizing adjuvant dexamethasone (Dex) +/− Thalidomide (Thal) and the second Dex + Bortezomib (Bort). AT was added at 2 or 3 months post-SCT for those with partial hematologic response or stable hematologic disease. We assessed the outcomes on these protocols with respect to AT-related mortality, hospitalizations in the first year post-SCT, immune recovery and OS. Sixty-four patients enrolled on these trials and 59 survived 2 to 3 months post-SCT to be evaluated for hematologic response. Seventeen were observed without AT while 42 received AT (10 Dex, 21 Dex+Thal, 11 Dex+Bort). There were no deaths due to AT. Thirteen of the 42 patients receiving AT (31%) were hospitalized during the first year post-SCT (6 with pneumonia [5 viral, 1 fungal]; 1 with sinusitis and S. pneumo bacteremia; 3 with congestive heart failure; 2 with pulmonary emboli; 1 with avascular necrosis of the hip) as compared to 2 hospitalizations (1 with engraftment syndrome; 1 with diarrheal illness) in the 17 patients not receiving AT (12%; p= 0.23 by χ2). At 1 year post-SCT median absolute lymphocyte counts (ALC) and IgG levels were lower in the AT group (ALC: 1.0 (0.4–2.9) vs 1.7 (0.9–5.1), p=0.01; IgG: 569 (205–1650) vs 867 (635–1200), p=0.04, two-tailed Mann-Whitney), and IgA recovery at 1 year was impaired in the AT group as well (p=0.07). Twenty-four of the 42 patients receiving AT (57%) had improved hematologic responses, including 10 of 11 patients receiving Dex+Bort, with 13 of 42 achieving CR (31%). Median overall survival has not been reached for those with CR to SCT and is 59 months for those who received AT (p=0.06). In sum, AL patients in this series receiving early AT post-SCT were more frequently hospitalized in the first year and had impaired immune recovery. However, over half of the AT patients had improved hematologic responses and, as a cohort, the median overall survival of AT patients was more than twice that of historical controls receiving SCT followed by observation alone.

Topics:
autologous stem cell transplant, immunologic adjuvants, pharmaceutical adjuvants, primary amyloidosis, immunoglobulin g, thalidomide, adjuvant therapy, bacteremia, bortezomib, chemotherapy regimen

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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