Single-dose pegylated-filgrastim versus daily filgrastim after high-dose chemotherapy and autologous stem cell transplantation for lymphoid malignancies: delayed platelets recovery?

Abstract

Dear Sir, High-dose chemotherapy, with or without radiotherapy, followed by autologous haematopoietic stem cell transplantation (HSCT), has a key role in the treatment of haematological malignancies. Granulocyte colony-stimulating factor (G-CSF) seems to reduce the duration of neutropenia and related infectious complications, although recent data1 have challenged some of the evidence of the previously reported advantage of G-CSF use in this setting. Pegylated filgrastim (Peg-G-CSF) has been shown to be as safe and as effective as daily filgrastim or lenograstim (daily-G-CSF) for mobilisation of progenitor cells from the bone marrow into the peripheral blood and for the management of standard chemotherapy-induced neutropenia, as well as high-dose chemotherapy followed by autologous2,3 or allogeneic HSCT4; however, a recent paper by Romeo et al.5, while presenting the comparison between different lenograstim doses for peripheral blood progenitor mobilisation with regards to both target CD34+ cell dose and autologous HSCT outcome, mentioned a delay in platelet recovery after Peg-G-CSF-stimulated transplantation compared with lenograstim-stimulated transplanation. We started to use Peg-G-CSF in our centre in October 2004 and an initial analysis in October 2006, published in the form of Poster at the 2007 Italian Society of Haematology (SIE) annual congress, revealed a delay in platelet recovery among 17 Peg-G-CSF- treated patients when compared with a matched historical control group treated with daily G-CSF (median day for platelet recovery >20 ×109/L: day +12 versus day +15 for patients treated with daily-G-CSF and Peg-G-CSF, respectively; p=0.03). Nevertheless, starting from January 2008, patients undergoing high-dose chemotherapy and autologous HSCT were assigned to receive either Peg-G-CSF (6 mg sc day +6) or daily-G-CSF (5 mg/kg/day sc or iv also starting on day +6). From January 2008 to August 2010, 49 patients were treated. Their median age was 58 years (range, 21–69 years). The diagnosis was non-Hodgkin's lymphoma in 14 patients, Hodgkin's lymphoma in 6 patients and multiple myeloma in 29. The median dose of infused CD34+ cells was 4.2×106/kg, collected after mobilization with chemotherapy (IEV, IGEV, DHAP, CTX) and daily-G-CSF. The conditioning regimen was BEAM in 19 patients, high-dose melphalan in 24 and other regimens in the remaining 6 patients. The groups of patients receiving Peg-G-CSF or daily G-CSF were matched for sex, age, diagnosis, state at transplantation, conditioning regimen and infused CD34+ cell dose. No differences were found between the two groups with regards to median time to reach an absolute neutrophil count greater than 0.5×109/L, platelet count greater than 20×109/L or platelet count greater than 50×109/L (Table I). Transfusion requirements, episodes of infection, duration of antibacterial or antifungal therapy and time to discharge were similar in the two groups. Table I Engraftment after autologous HSCT in the two groups of patients. These data, although limited, suggest that both Peg-G-CSF and daily G-CSF can support haematopoiesis after autologous HSCT with similar engraftment outcomes. A delay in platelet reconstitution, as reported from our preliminary experience and in the paper by Romeo et al.5, was not confirmed. Larger, randomised studies are needed to definitely detect the hypothesised differences between the outcomes of the two approaches.