Standard Versus High Dose Lenograstim in Adults with Hematological Malignancies for Peripheral Blood Progenitor Cell Mobilization: Results of a Retrospective Study on Behalf of Rome Transplant Network.

PURPOSE: The aim of this retrospective study was to compare 5 vs 10 mcg/kg/day of lenograstim (Leno) (Myelostim 34®) in collecting target dose of CD34+ peripheral blood progenitor cells (PBPC) in adults candidate to autologous transplant. Univariate and multivariate analysis were carried out in order to identify factors predicting for satisfactory procedures.

Material and Methods: From 01/’04 to 06/’08, 166 consecutive patients from 2 Institutions participating to the Rome Transplant Network with acute leukemias in complete remission (AL, #28), lymphomas (#77) and multiple myeloma (MM, #61) underwent 182 CD34+ PBPC mobilization procedures with Leno following standardized regimens. Only the 1^st procedure for each patient was considered for the analysis. The target dose of CD34+ cells was ≥ 2 x10⁶/kg for AL, ≥ 4 for lymphomas and ≥ 8 for MM with Leno starting at day +19, +1 and +5 from the end of chemotherapy, respectively. Eighty-seven patients received 5 mcg/kg Leno subcutaneously once a day (Leno5 cohort), while 79 patients were given Leno twice a day for a total dose of 10 mcg/kg (Leno10 cohort). Quantitative variables were compared by using analysis of variance (ANOVA); for qualitative parameters we used the chi-square test. A multivariate logistic model was used to analyze associations between some baseline characteristics and effectiveness to reach the required CD34+ cell target dose. Linear analysis was used to determine the relative significance of the same characteristics as predictive variables for stimulation length. Enter and remove limits were p=0.10 and 0.15, respectively. The SPSS (13.0) statistical program was used for analysis.

Results: Age, sex, diagnosis and relative target dose, previous therapy including fludarabine, radiotherapy, number of previous chemotherapy regimens were not significantly different between the 2 cohorts. No statistically significant difference was observed in terms of number of apheresis performed, amount of blood processed, total number of CD34+ PBPC x10³/mL mobilized and CD34+ cells x10⁶/kg collected between the 2 cohorts. Reaching of the target dose and stimulation length are reported in table by Leno dose administered.

Forty-one patients did not reach the cell target. Of these, 16 underwent in any case PBPC transplant with the CD34+ cell dose collected. Of the remaining 25 patients, 9 were excluded from further attempts of PBPC mobilization, while 16 underwent 1 or 2 additional procedures and 10 of them were later transplanted. Overall, of 166 patients, 151 [Leno5 #76 (87%), Leno10 #75 (95%); p=ns] were able to be submitted to transplant. No Leno-related adverse event was observed in both the patient cohorts. In multivariate analysis, factors predicting for reaching the required CD34+ cell target dose were sex, with a negative impact of female sex (p=0.028), and Leno dose, with a positive impact of high dose, although exclusively restricted to MM patients (p=0.05). Finally, the multivariate analysis identified previous therapy not including fludarabine as the only factor significantly correlated with a shorter stimulation length (p=0.002).

Conclusion: High dose Leno showed a higher capacity of harvesting only in MM patients for whom the CD34+ cell target was the highest to be collected. Leno dose did not impact on the CD34+ cell collection for AL and lymphoma patients as well as on the proportion of autologous transplants finally performed. As previously reported in healthy donors, in our study patient sex was an independent predictive factor for reaching the required CD34+ cell dose. Finally, fludarabine negatively influenced the length of Leno administration.