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Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

BACKGROUND Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS Same‐day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next‐day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14‐ or 20‐hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change −0.034%; p < 0.01). CONCLUSION Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.

Increased transplant activity calls for improved stem cell collection, especially when peripheral blood is the preferred source of haematopoietic progenitor cells (HPCs).Plerixafor is a bicyclam molecule that mobilizes CD34+ cells by reversibly disrupting CXCR4-CXCL12-supported HPC retention. Plerixafor is given with granulocyte colony-stimulating factor (G-CSF) to help harvest autologous CD34+ cells for transplantation when mobilization with G-CSF fails. Mobilization protocols with the same doses of plerixafor and G-CSF have been used off-label in healthy allogeneic donors, with equal success and scarce side effects, both in adult and paediatric patients.Plerixafor has also been used as a sole mobilization agent. Plerixafor alone or coupled with G-CSF might lead to harvesting distinct cellular populations conferring improved engraftment properties and increased survival. Those characteristics might make plerixafor an especially attractive mobilization agent, particularly for non-related donations. However, available data are limited, and long-term follow-up is needed to clarify the best scenario for using plerixafor with or without G-CSF in healthy donors.In this review, we will summarize the evidence supporting this practice, highlighting the practical aspects and providing clues for an expanded use of plerixafor.