Very large amounts of peripheral blood progenitor cells eliminate severe thrombocytopenia after high-dose melphalan in advanced breast cancer patients

Abstract

Summary:We analyzed the relationship between the reinfusion of large or very large amounts of peripheral blood progenitor cells (PBPC) and hematologic toxicity in twentyone advanced breast cancer patients subjected to a myeloablative dose of melphalan at the end of a high-dose sequential chemotherapy (HDSC) program. We also evaluated the influence of the white blood cell (WBC) count to predict an optimal PBPC harvest after highdose chemotherapy and growth factor priming. Twentyone patients with high-risk or metastatic breast cancer sequentially received: high-dose cyclophosphamide (HD-Cy) and In conclusion, our data suggests that V-LA-CD34 + eliminates severe thrombocytopenia and platelet transfusion requirements in breast cancer patients subjected to HD-L-PAM, and higher PBPC collections seems to coincide with WBC count higher than 20 × 10 9 /l after HD-Cy and G-CSF mobilization. These results justify a prospective study to establish whether large doses of CD34 + cells result in significant clinical benefits.

International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)

“…Benedetti et al and Ketterer et al have reported that very large numbers of CD34 þ cells/kg (415 million CD34 þ cells/kg) after high-dose melphalan administration can eliminate severe thrombocytopenia and platelet transfusion requirements. 12,13 In most studies, CD34 dose was not associated with different outcomes with the exception of a retrospective study performed by Oran et al 14 demonstrating that increasing CD34 doses were associated with improved outcomes in patients with amyloidosis who underwent ASCT. Thus, although retrospective analysis suggests a strong dose-response relationship between CD34 þ cell dose and rate of neutrophil and platelet recovery after myeloablative therapy, the impact of the benefit has been small.…”

Peripheral blood progenitor cell collection after epirubicin, paclitaxel, and cisplatin combination chemotherapy using EPO‐based cytokine regimens: a randomized comparison of G–CSF and sequential GM–/G–CSF

“…At the present time, the combination of chemotherapy and growth factors represents the most effective PBPC mobilization strategy in cancer patients. The number of precursor cells (namely, CD34+ cells) in PBPC collections predicts the speed of neutrophil and plt engraftment after high‐dose chemotherapy/PBPC return, so that G–CSF has been widely employed to enhance the ability of cytoreduc‐tive chemotherapy of mobilizing PBPCs 9–16 . In fact, the reduction of chemotherapy‐induced neutropenia and the enhancement of chemotherapy‐elicited PBPC mobilization represent the clinical effects through which this cytokine plays a substantial role in the treatment of cancer patients.EPO exerts its clinical effect by increasing erythroid production in neoplastic patients in whom cisplatin‐based chemotherapy has blunted EPO production by renal cells 40–44 .…”

“…Accelerated recovery consists of a rapid increase in neutrophil and platelet counts 4–10 . The CD34+ cell dose administered determines, in part, the success of the engraftment 9–16 . Because of the difficulty in obtaining adequate PBPCs in the steady state, mobilization strategies have been developed to increase the pool of circulating HPCs and decrease the total number of apheresis procedures.…”

Increased mobilization and yield of stem cells using plerixafor in combination with granulocyte-colony stimulating factor for the treatment of non-Hodgkin’s lymphoma and multiple myeloma

“…Of note in the latter study, patients who required 2 apheresis procedures to collect >2.5 × 10 6 CD34+ cells/kg had slower platelet engraftment independent of the CD34+ cells dose, suggesting that qualitative differences in CD34+ cells collected may be important 22. While other studies have shown that very high doses of CD34+ cells (>15 × 10 6 /kg) can significantly reduce or eliminate severe thrombocytopenia and platelet transfusion requirements,23,24 it remains uncertain whether this additional benefit is outweighed by the increased resources required to collect such a large number of progenitors. Collectively, these data have been used to support practice patterns targeting a minimal CD34+ cell dose of 2.0 × 10 6 /kg, and an “optimal” dose of 4 to 6 × 10 6 /kg for a single transplant 25,26…”