Showing papers by "Todd E. DeFor published in 1999"

Risk factors for severe hemorrhagic cystitis following BMT.

Abstract: Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graft-versus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P < 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna.

High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths.

Abstract: Interleukin 10 (IL-10) is a potent inhibitor of proliferative T cell responses toward alloantigens, and suppresses the production of pro-inflammatory cytokines which are important in cellular activation and recruitment to sites of inflammation. Because of these properties, we hypothesized that high IL-10 production in patients prior to BMT may predict a better outcome. To investigate this, peripheral blood mononuclear cells (PBMNC) were obtained from 58 recipients (11 autologous, 25 related donor (RD), and 22 unrelated donor (URD)), prior to conditioning therapy. PBMNC were cultured for 24 h in the presence and absence of lipopolysaccharide (LPS) and culture supernatants were assayed for IL-10 using an ELISA method. Spontaneously produced and LPS-stimulated IL-10 levels were correlated with the development of transplant-related complications (TRC) including grade II-IV acute GVHD, veno-occlusive disease, idiopathic pneumonia syndrome and multi-organ dysfunction syndrome, and with death before day 100. For the autologous group, there were no TRC and only one death prior to day 100; therefore, no statistical comparisons to IL-10 levels could be made. In the RD group, 36% developed one or more TRC and 24% died before day 100; however, there were no statistically significant associations between spontaneous or LPS-induced IL-10 levels. In URD patients 41% developed TRC and 55% died prior to day 100. In this group, higher levels of spontaneous IL-10 production were associated with a lower overall occurrence of TRC (P = 0.03) and early death (P = 0.04). Our data would indicate that higher levels of IL-10 production prior to URD BMT may predict fewer TRC, as well as early deaths. The hypothesis that high IL-10 production prior to BMT may decrease complications following URD BMT warrants further testing.

Autologous stem cell transplantation for high-risk pediatric solid tumors.

Abstract: Many solid tumors exhibit a steep dose-response to alkylating agents, and autologous stem cell transplantation (ASCT) allows escalation of the chemotherapy dose for treatment of high risk solid tumors. We have transplanted 24 children and young adults with relapsed or metastatic solid tumors on two consecutive ASCT protocols consisting primarily (protocol MT 8911) or exclusively (MT 9408) of alkylating agents. The median time to neutrophil engraftment was 21 days in protocol MT 8911 (no prophylactic use of growth factors) and 14 days in MT 9408 (G-CSF, 5 microg/kg, started on day 0). Disease-free survival estimated by the Kaplan-Meier method is 39% (95% CI: 19-59%) at 2 years after transplant and 34% (95% CI: 14-54%) at 4 years after transplant. Six of the nine patients with metastatic or relapsed disease that were transplanted while in complete remission (four patients with Ewing's sarcoma family of tumors and two patients with anaplastic Wilms tumor) are alive and disease-free with a median follow-up of 37 months (range 20-74 months). The estimated 4 year survival for patients receiving a transplant while in high risk remission was 78% (95% CI: 51-100%). In contrast, 13/15 patients that were transplanted while in partial remission died because of progressive disease or transplant-related complications. There were three transplant-related deaths (12.5%), including one patient with multiorgan failure, and two patients with complications of hepatic veno-occlusive disease. Our data indicate that autologous stem cell transplantation should be considered for consolidation therapy of high risk and relapsed pediatric patients with solid tumors who have achieved complete remission.