Fractionated Stem Cell Infusions for Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant

High dose therapy with autologous stem cell transplant (SCT) is an established therapeutic modality for multiple myeloma (MM). Although effective, it is associated with significant symptom burden due to the obligate period of neutropenia in addition to an increased risk of infectious complications. In animal models, infusing stem cells over a period of days enhances immune reconstitution (Felfly H, et al. Br J Haematol. 2009; 148: 646–658). We hypothesized that multiple stem cell infusions could reduce the period of neutropenia and enhance immune recovery resulting in a better tolerated procedure.

We are conducting a phase II trial of multiple fractionated autologous stem cell infusions after high-dose Melphalan. We compared initial engraftment kinetics of the first 14 patients to receive multiple infusions (Days 0, +2, +4, +6) after high-dose Melphalan (study group) to 23 patients receiving high-dose Melphalan followed by the standard single stem cell infusion (Day 0) (standard group). Pegfilgrastim was given to all patients on Day +1. All patients underwent SCT between October 2011 and July 2012.

Results are shown in Table 1. Similar numbers of stem cells were collected in the study and standard groups. The total number of stem cells infused was 9.7 × 10^∧6 CD34+ cells/kg in the study patients compared to 5.0 × 10^∧6 CD34+ cells/kg in the standard patients. To date, the median duration of neutropenia (days of ANC < 500) and lymphopenia (days of ALC < 500) as well as the days to neutrophil, lymphocyte and platelet engraftment are similar. There are no significant differences in the number of red cell or platelet transfusions, days of fever, diarrhea, empiric antibiotics or documented infections. Despite receiving multiple infusions, none of the patients in the study group experienced an infusion reaction. Engraftment syndrome occurred in 3/14 (21%) of the study patients. The median duration of hospitalization was 15 days in the study cohort versus 17 days in the concurrent control group (P = 0.01).

Multiple stem cell infusions following high dose Melphalan in patients with MM were not associated with a higher incidence of adverse side effects from DMSO nor unexpected frequency of engraftment syndrome. Fractionating stem cells over a period of days may result in less antibiotic use, reduced frequency of infection and was associated with shorter hospitalizations. We continue to collect patient reported symptom scores in order to determine if we can improve patient experience during SCT.

Table 1.

Immune and clinical parameters in standered and study patients

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No relevant conflicts of interest to declare.