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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.

A case-controlled analysis was performed to assess the effect of stem-cell source on autograft in a group of patients with malignant lymphoma reported to the European Bone Marrow Transplant Group (EBMT). The study was performed matching 83 patients autografted with peripheral blood stem cells (PBSC) with 83 autologous bone marrow transplantation (ABMT) patients. The case-matching was carried out following selection of the main prognostic factors for progression-free survival by multivariate analysis. The progression-free survival was similar in both types of transplants (38.5% PBSCT vs. 36.4% ABMT). The overall relapse and progression rate for the PBSCT was 51.2% compared with 50.1% for the ABMT patients. The differences were not significant statistically. The transplant-related mortality was 6% for both groups. The neutrophil and leucocyte recovery occurred faster in the peripheral blood stem-cell transplantation (PBSCT); the platelet recovery was not significant. A higher number of interstitial pneumonitis and fungal infection episodes were observed in the ABMT group. In conclusion, in these closely matched groups, there is no difference in PFS between patients undergoing PBSCT and those undergoing ABMT. However, the patients autografted with PBSC have a more rapid engraftment and a lower toxicity.

We report the preliminary results of a study exploring the possibility of collecting circulating progenitor cells (PBSC) with a protocol based on the administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10-micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+ cells occurred after a median of 10 days (range 8-11), generally coinciding with the median peak level of CFU-GM, with a mean 31.27 fold increase above basal levels. 3 (range 2-5) leukaphereses were required to harvest a median number of 25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC yield. In transplanted patients, a strong correlation was found between CD34+ cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was observed and apheretic procedures were regularly performed outpatiently. Our conclusion is that this protocol is particularly suitable for an outpatient treatment/collection program.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.

A case of localized Trichosporon beigelii infection is reported in a 40-year-old woman with Ph+ chronic granulocyte leukemia who underwent autologous blood stem cell transplantation. On day +14 after autograft, while severely neutropenic, she developed a local infection involving the soft tissues surrounding the central venous catheter (CVC) point of entry into the subclavian vein. Trichosporon beigelii was isolated from culture of the CVC tip; resolution occurred after removal of the CVC, neutrophil recovery and antifungal treatment with amphotericin B and 5-fluorocytosine. To our knowledge this is the first case of CVC localized infection from Trichosporon beigelii after transplantation.