Number Of Apheresis Days To Reach Target Stem Cell Dose May Be a Predictor Of Secondary Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Autologous stem cell transplantation (ASCT) is an effective consolidation therapy for patients with relapsed/refractory Hodgkin's and Non-Hodgkin's lymphoma. Studies have shown that infusion of at least 2 × 10⁶ CD34⁺ cells/kg recipient body weight is required for reliable neutrophil and platelet engraftment. However there is no published data on the impact of number of apheresis days required to reach the target stem cell dose and incidence of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).

Consecutive patients who underwent ASCT at M. D. Anderson cancer center from January 2008-July 2011 for Hodgkin's or Non-Hodgkin's lymphoma were evaluated to assess the impact of duration of mobilization on the incidence of secondary MDS/AML. Baseline patient, disease, and transplant characteristics including number of days of mobilization needed to collect target cell dose of 5 × 10⁶ CD34⁺ cells/kg. The median number of days to reach target was 2 (range 1-5) days. We used the median as cut off to classify patients as slow (> 2 days) or fast (≤ 2 days) mobilizers. The cumulative incidence of secondary MDS/AML was estimated considering death preceding a secondary malignancy as a competing event. Cox's proportional hazards regression analysis was used to evaluate predictors of the rate of secondary MDS/AML.

A total of 283 patients underwent ASCT during the study period. 153 of these patients were classified as fast mobilizers and 130 patients as slow mobilizers. Indication for transplant, disease status prior to transplant, age and gender distribution are as shown in Table 1. Twelve patients were diagnosed with secondary MDS/AML after a median follow-up of 39 (range 2-64) months. Only one of these patients had pre-existing pretransplant cytogenetic abnormalities (monosomy 7 in one metaphase). Nine of 12 cases were diagnosed within 3 years post-transplant. On univariate analysis, days to target stem cell dose was the only predictor of the rate of secondary MDS/AML. The rate of secondary MDS/AML within 3 years post-transplant was higher in the slow mobilizer group (n=8, 6% cumulative incidence at 3 yrs) compared with the fast mobilizer group (n=4, 1 % cumulative incidence at 3 yr, HR=0.2, P value 0.05) Figure 1. None of the remaining factors listed in Table 1 were found to be associated with the rate of secondary MDS/AML on univariate analysis. In patients who did not have active disease at transplant, overall survival tended to be higher in the fast mobilizer group compared with slow mobilizers. However, this effect did not reach statistical significance on multivariate analysis (hazard ratio of 0.6; with P value of 0.1). Absolute neutrophil count of > 500/mm³ was achieved at a median of 10 days in fast mobilizers versus 11 days in slow mobilizers (P value 0.000). Similarly platelet count >20,000 was achieved sooner in fast mobilizers at a median of 11 versus 12.5 days in slow mobilizers (P value 0.000).

Number of apheresis days required to collect target stem cell may be a predictor of secondary MDS/AML. There is a trend towards better survival among patients who mobilize in two or less than two days. As expected fast mobilizers have quicker neutrophil and platelet engraftment.

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Qazilbash:Millennium: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees.