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Presents a study that examined the association of etoposide mobilization with a significant incidence of neutropenic fever. Information on the effectiveness of etoposide for peripheral blood progenitor cell (PBPC) mobilization; Role of PBPC mobilization in PBPC transplantation; Impact of the granulocyte-colony stimulating factor in mobilizing CD34 cells.

Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients. Bone Marrow Transplantation (2001) 28, 491–495. [ABSTRACT FROM AUTHOR]

Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic malignancies were treated with twice daily TBI using a high-energy source (18–24 MV). The first patient cohort (n = 11) received a total dose of 14.4 Gy in nine fractions, and the second cohort (n = 5) received doses escalated to 15.3 Gy. All patients received high-dose etoposide (60 mg/kg) and allogeneic stem cell transplantation following the TBI. All patients had HLA-identical sibling donors. The median times for neutrophil and platelet engraftment were 13.5 and 12 days, respectively, and did not differ between the two cohorts. All but one patient developed treatment-related grade 3 or 4 mucositis. There were three cases of grade 4 pulmonary toxicity and three cases of grade 4 hepatic toxicity among the 14.4 Gy cohort, and one case each of grade 4 pulmonary and hepatic toxicities among the 15.3 Gy cohort. In most cases comorbid conditions contributed to these toxicities. Two patients had significant GVHD of the GI tract. Six relapses occurred, five (45%) in the 14.4 Gy cohort and one (20%) in the 15.3 Gy cohort. The 100-day treatment-related mortality rates were 9% and 20% for the 14.4 Gy and 15.3 Gy cohorts, respectively, and the median survivals were 226 and 201 days, respectively. We conclude that TBI dose escalation above the previously used 13.5 Gy dose is feasible using a high-energy source and high-dose etoposide. Acute and chronic toxicities were primarily related to GVHD, infection and relapse rather than to TBI. Bone Marrow Transplantation (2000) 25, 807–813. [ABSTRACT FROM AUTHOR]

Therapy-related myelodysplastic syndrome (t-MDS)/ acute myeloid leukemia (t-AML) has been reported after autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT) for various malignancies. We retrospectively reviewed all adult ABMT/PBSCT cases performed at the University of Chicago Medical Center from 1985 to 1997 in order to determine the incidence of therapy-related leukemia. Among 649 patients, seven (1.1%) developed therapy-related acute lymphoblastic leukemia (one patient) or t-MDS/t-AML (six patients). Of these seven, primary malignancies included one case of breast carcinoma, five cases of Hodgkin’s disease (HD) and one case of non-Hodgkin’s lymphoma (NHL). Disease-specific incidences for therapy-related leukemia occurring after ABMT/PBSCT were one in 354 (0.3%) for breast carcinoma, five in 79 (6.3%) for HD and one in 103 (1%) for NHL. The median latency periods for the development of therapy-related leukemia from the time of initial diagnosis and of ABMT/PBSCT were 5.5 and 1.5 years, respectively, for the combined HD and NHL group of patients and 4.4 and 2.8 years, respectively, for the one breast carcinoma patient. All seven patients had clonal cytogenetic abnormalities, and five had recurring abnormalities typical of myeloid disorders. Given the similar latency period observed in patients treated with conventional chemotherapy alone, our findings support the hypothesis that therapy-related leukemia after ABMT/PBSCT likely results from pre-transplant therapy. Early detection of therapy-related leukemia is therefore critical to exclude these patients from undergoing ABMT/PBSCT. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy (HDC) with autologous stem-cell support (ASCS) has been investigated in patients with cisplatin-resistant, relapsed, or poor-prognosis germ cell tumor (GCT). Although some of these patients have benefited from this approach, it is unknown when best to administer such therapy. This review categorizes the HDC/ASCS trials into those performed as (1) salvage therapy for second or greater relapse, (2) salvage therapy for first relapse, and (3) first-line therapy. From the trials performed to date, earlier use of HDC/ASCS (first-line or salvage therapy in first relapse) achieved a higher durable remission rate than when used later as salvage therapy in second or greater relapse (approximately 50% v 15%, respectively). HDC/ASCS is not beneficial for relapsed or cisplatin-resistant primary extragonadal GCT patients, but may have a role in testicular GCT who are not "absolutely" cisplatin-resistant. Trial differences regarding the patients selected and the high-dose transplant preparative regimen used have made precise comparative analyses difficult. There has been only one phase III trial and it did not show a survival advantage to the HDC/ASCS arm, although this trial had significant methodological difficulties. In the future, more definitive treatment recommendations may be made upon completion of two ongoing phase III trials comparing HDC/ASCS with standard chemotherapy in the first salvage and front-line settings.