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BACKGROUND: High dose MEL with auto SCT is an established therapeutic modality for MM. Although effective, it is associated with significant symptom burden due to the obligate period of neutropenia and increased risk of infection. In animal models, infusing stem cells (SC) over a period of days enhances immune reconstitution (Felfly H, et al. 2009). Multiple SC infusions could reduce the period of neutropenia and enhance immune recovery resulting in a better tolerated procedure. METHODS: We are conducting a phase II trial of multiple fractionated auto SC infusions after high-dose MEL. We compared initial engraftment kinetics after high-dose MEL of the first 14 pts to receive multiple infusions (Days 0, +2, +4, +6) (study group) to 23 pts receiving the standard single SC infusion (Day 0) (standard group). Pegfilgrastim was given on Day +1 and SCT was between October 2011 and July 2012 in all pts. RESULTS: Table 1. Similar numbers of SCs were collected in both groups. The number of SCs infused was 9.7 x 10^6 CD34+ cells/kg vs 5.0 x 10^6 CD34+ cells/kg in study and standard pts. To date, the median duration of neutropenia (days ANC < 500) and lymphopenia (days ALC < 500), and days to neutrophil, lymphocyte and PLT engraftment were similar. There were no significant differences in the number of red cell or PLT transfusions, days of fever, diarrhea, empiric antibiotics or documented infections. Despite multiple SC infusions, none of the pts in the study group experienced infusion reaction. Engraftment syndrome (ES) occurred in 3/14 of study pts. Duration of hospitalization was 15 days in study pts vs 17 days in the concurrent control group (P = 0.01). CONCLUSIONS: Multiple SC infusions after high dose MEL in pts with MM were not associated with increased adverse effects from DMSO or unexpected frequency of ES. Fractionating SCs over a period of days may result in less antibiotic use, reduced infection and was associated with shorter hospital stay. We continue to collect pt reported symptom scores to determine if we can improve pt experience during SCT.
Table 1. Immune and Clinical Parameters
Standard group (N=23) Med (range)
| Study group (N=14) Median (range)
| |
CD 34+ cells collected (x 10^6/kg)
| 11.7 (5.1 - 20.7)
| 13.0 (10.1 -28.0)
|
CD 34+ cells infused (x 10^6/kg)
| 5.0 (3.2 - 8.3)
| 9.7 (7.0 – 14.0)
|
Duration of ANC < 500 k/mL (days) | 4 (3 - 9)
| 4 (3 - 5)
|
Time to neutrophil engraftment (days)
| 10 (8 - 14)
| 10 (9 - 11)
|
Duration of ALC < 500 k/mL (days) | 14 (5 - 22)
| 14 (12 - 23)
|
Time to lymphocyte engraftment (days)
| 14 (9-21)
| 13 (11-22)
|
Time to PLT engraftment (days)
| 13 (0-17)
| 13.5 (10-20)
|
# of RBC Transfusions
| 0 (0 - 8)
| 0 (0 - 3)
|
# of PLT Transfusions
| 2 (0 - 12)
| 1 (1 - 4)
|
Days of T ≥ 38 deg C
| 1 (0-8)
| 0 (0-7)
|
Days on empiric/directed antibiotics
| 5 (0 - 28)
| 0 (0 - 14)
|
Infections, N (%)
| 7 (30)
| 1 (7)
|
Days of diarrhea ≥ 500cc
| 0 (0-3)
| 0 (0-7)
|
Pts with ES, N (%)
| 0 (0)
| 3 (21)
|
Pts with infusion reactions, N (%)
| 2 (9)
| 0
|
Duration of hospitalization (days)
| 17 (13 - 36)
| 15 (13 - 19)
|