The treatment of AL amyloidosis in the Netherlands in 2013

AL amyloidosis is the only form of amyloidosis caused by a small plasma cell clone in the bone marrow. The produced aberrant free light chain forms, together with serum amyloid P, deposits in several organs leading to organ dysfunction. Involvement of the heart is the most important prognostic factor. Treatment of systemic AL amyloidosis is based on treatments as used in multiple myeloma, however is much more complicated due to organ dysfunction and worse clinical condition of the patients. Aim of treatment is to achieve a complete haematological response. Organ responses can occur later on. High dose melphalan followed by stem cell transplantation is given to younger en fit patients. Older patients are treated with oral melphalan and dexamethasone. Bortezomib also seems to be well tolerated by patients and has good clinical efficacy. Several randomised phase III studies, such as the HOVON 104, have started to investigate superiority of treatment with proteasome inhibitors. Treatment of patients in clinical studies is highly recommended

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor

Background: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 106/L on 2 consecutive days accompanied by increasing white blood cells.  Study Design and Methods: In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies.  Results: In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 106/L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 106/L) circulating CD34+ cell counts the success rate was 44.2%.  Conclusion: Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor

Background: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 106/L on 2 consecutive days accompanied by increasing white blood cells.  Study Design and Methods: In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies.  Results: In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 106/L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 106/L) circulating CD34+ cell counts the success rate was 44.2%.  Conclusion: Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach

2009

ABSTRACT Methods Study design and end points In this prospective multicenter phase II study, the effect of three courses of vincristine, doxorubicin, dexamethasone (VAD) administered as rapid infusion 9,10 followed by HDM with ASCT was evaluated in AL amyloidosis. Patients who did not meet the eligibility criteria for HDM after VAD went off protocol treatment and were followed for survival. Study end points were efficacy with regard to response rate, overall survival, feasibility and the value of risk factors at diagnosis. The trial was carried out in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Boards of all participating hospitals, and all patients provided written informed consent before inclusion in the study