Higher Stem Cell Dose Infusion after Intensive Chemotherapy Does Not Improve Symptom Burden in Older Patients with Multiple Myeloma and Amyloidosis

Abstract

Autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM) is associated with high symptom burden, particularly for older patients and those with amyloid light-chain (AL) amyloidosis. Symptom burden peaks during leukopenia. We hypothesized that higher doses of CD34+ stem cells would be associated with an improved symptom outcome. Patients undergoing ASCT for MM who were ≥60 years old or had AL amyloidosis were randomized to receive either a standard (4–6×106 cells/kg) or high dose (10–15×106 cells/kg) of CD34+ cells after melphalan 200 mg/m2. Symptom burden was assessed via the MD Anderson Symptom Inventory MM module (MDASI-MM). Eighty patients were enrolled. Median CD34+ cell doses were 5.1×106 cells/kg (standard dose) and 10.5×106 cells/kg (high dose). The most severe symptoms during the first week were fatigue, lack of appetite, drowsiness, disturbed sleep, and pain. The AUC for the mean composite severity score of these symptoms was similar between treatment arms (P = .819). Median times to neutrophil, lymphocyte, and platelet engraftment were also similar between groups. IL-6 increased similarly for both groups throughout the ASCT course. Infusion of higher autologous stem cell dose after high-dose chemotherapy does not yield a difference in symptom burden or engraftment time in the first few weeks post-ASCT.

High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…It should be also noted, that in the first and only randomized trial looking at CD34 dose and outcome in an autologous setting higher stem cell dose (10-15 × 10 6 /kg vs . standard 4-6 × 10 6 /kg) did not yield a difference in post-transplant symptom burden or engraftment time [ 18 ].…”

Health-Related Quality of Life after Autologous Stem Cell Transplantation for Multiple Myeloma

“…Acupuncture has been shown to reduce symptom burden during ASCT and at day 15 and 30 after transplantation in a sham-controlled trial 44 . Increased stem cell infusion dose has been tested in a RCT and did not seem to have any impact on symptom burden in patients with MM or amyloidosis undergoing ASC 45 . Since the median OS in MM is increasing with the availability of new drugs, studies with longer follow-ups are needed to measure longitudinal HRQoL.…”

Low-dose peripheral blood stem cell graft after high-dose chemotherapy - an evaluation of hematopoietic reconstitution

“…Remarkably a further study showed that patients who received lower stem cell doses had an increased risk of > 3 days of absolute neutropenia, compared to patients who received higher stem cell infusions, while at a median follow-up of 51 months, there was no difference in survival between patients with absolute neutropenia > 3 days versus patients with absolute neutropenia for ≤3 days [39]. On the other hand, it was reported that for older MM patients undergoing HD chemotherapy and ASCT infusion of higher stem cell doses did not yield a reduction in symptom burden or engraftment time in the first weeks after ASCT [40]. Also in accordance to this study multiple, fractionated stem cell infusions (days 0, + 2, + 4, + 6) following HD melphalan did not enhance engraftment kinetics or significantly alter MM patients' clinical course following ASCT [41].…”