High Dose Cyclophosphamide: Stem Cell Mobilizing Capacity in 21 Patients

Abstract

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.

Optimization of Peripheral Blood Stem Cell Mobilization

“…Siena et al and Sutherland et al reported that patients who received CY + GM‐CSF‐stimulated PBSC had more rapid and consistent platelet recoveries as compared with CY mobilized or steady‐state PBSC alone [36,, 37]. During the recovery phase from chemotherapy, the amplitude of the circulating stem cell concentration is related to the intensity of the myelosuppressive agents used [28,, 30,, 32,, 36–, 39]. Intermediate‐dose CY (4 g/m 2 ) and G‐CSF had been used to collect stem cells on an outpatient basis, but higher doses of CY (7 g/m 2 ) are associated with higher stem cell yields [36–, 39].…”

“…During the recovery phase from chemotherapy, the amplitude of the circulating stem cell concentration is related to the intensity of the myelosuppressive agents used [28,, 30,, 32,, 36–, 39]. Intermediate‐dose CY (4 g/m 2 ) and G‐CSF had been used to collect stem cells on an outpatient basis, but higher doses of CY (7 g/m 2 ) are associated with higher stem cell yields [36–, 39]. Studies suggest that combinations of CY + etoposide (CE), CY + etoposide + cisplatin (CEP) or CY + Taxol ® are probably more effective at stem cell mobilization than CY alone [11,, 40,, 41].…”

Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization

“…23 Although cyclophosphamide 7 g/m 2 may represent a useful mean of increasing collection of PBSC, the toxicity is considerable with occurrence of fatal complications in 2/21 patients. 24 The collection of bone marrow cells under general anesthesia may be successful in some of those patients who have failed mobilization of peripheral stem cells. Since ABMT has been shown to be inferior to PBSCT in terms of time to engraftment and infectious complications, 11,12 alternative mobilization strategies are needed.…”