Hematopoietic Stem Cell Mobilization with Intermediate Dose Cytarabine

Hematopoietic stem cell (HSC) mobilization in patients with intention of autologous stem cell transplantation (ASCT) can be done using granulocyte colony stimulating factor (G-CSF) or combination of G-CSF with chemotherapy. The choice is often based on the characteristics of the patients, the desired number of stem cells and characteristics of the service. In developing countries, limitations of transplant centers include sending blood samples and apheresis bag to perform CD34 count and cell processing to laboratories far from the one that performed the collection, restriction of dates for apheresis, and use of apheresis machines that process low blood volumes, which require a mobilization protocol that allows the collection HSC under these conditions. We retrospectively analyzed the efficacy and safety of 69 consecutive mobilizations with cytarabine at dose of 1200 mg/m² and G-CSF in patients with hematologic malignancy and germ cell tumor in a stem cell transplant center in Brazil.

The median age of patients was 56 years (20-75), with 21% over 65 years old and 46 patients (66%) were male. Thirty seven patients were multiple myeloma, 17 patients with non-Hodgkin's lymphoma, 10 patients with Hodgkin's lymphoma, 4 patients with solid tumors and 1 amyloidosis. Most patients underwent mobilization for the first time (87%). Nine patients had already been mobilized previously, 6 patients for a second HSCT, two patients due to mobilization failure with G-CSF.

The percentage of patients who collected at least 2x10⁶ CD34 cells/kg was 95%, with 89% of patients requiring only 1 apheresis. Among the patients who were successful in the collection, 77% of the patients started the collection on the 16th day and 97% of the patients on the 17th day of mobilization. The median number of HSC collected was 11.68 x10⁶ CD34/kg and the number of CD34 cells in mobilized blood in the day before the apheresis was 85.13 cells/µl. The increase of the number of lines of treatment (p=0.04) and previous ASCT (p=0.01) negatively impacted the number of mobilized CD34 cells, with no difference in the collection success rate in patients undergoing a second ASCT, successfully in 5 of 6 patients mobilized (p=0.24). Although the collection success rate was lower in patients with non-Hodgkin lymphoma, 88.24% versus 97% in patients with multiple myeloma and 100% in patients with Hodgkin lymphoma and solid tumors, the small number of failures may not have been able to reveal statistical relevance (p=0.3685). Similarly, there was no difference when was used an apheresis machine that processes low or high volumes (p=0.28).

The dosage of lymphomononuclear cells above 1000 cells/µl correlated with the success of the collection (p=0003) and could replace the count of CD34 cells in services that do not have cytometry or carry out the measurement of the sample with a long interval between collections. Thrombocytopenia grade 3 or 4 was observed in 6% of the patients, with 3% of platelet transfusion. Red blood cell transfusion was required in 11% of patients and febrile neutropenia was not observed.

We conclude that intermediate dose of cytarabine is highly effective, predictable and relatively safe in promoting HSC mobilization, and can be used in centers in developing countries and high risk failure patients, contributing to the expansion of services that perform HSCT

No relevant conflicts of interest to declare.