For patients undergoing stomatotoxic HSCT regimens, GM-CSF may reduce the duration of oral mucositis, but is unlikely to effect the severity of oral mucositis or risk of airway compromise, and the severity of mucositis is likely to remain dose-limiting.
Summary:Organ system dysfunctions are frequent complications of hematopoietic stem cell transplantation (HSCT), including allogeneic or autologous bone marrow transplantation Circulating anticoagulants protein C (PC) and antithrombin III (AT) are markers of, and possibly (BMT), and peripheral blood stem cell transplantation (PBSCT). The occurrence of single organ system dysfuncinvolved in the pathogenesis of, significant organ dysfunction, in patients undergoing autologous peripheral tion in the post-transplant period has been shown to predict for subsequent development of multiple organ dysfunction blood stem cell (PSBC) or autologous bone marrow (BM) transplantation. The effect of the stem cell source, and for death. 1,2 Single and multi-organ dysfunction may be due to the culmination of an uncontrolled inflammatory the use of hematopoietic growth factors (GFs), and the specific preparative regimen on the incidence of organ response to some initial event, mediated by an as yet incompletely understood interplay of cytokines, compsystem dysfunction or on post-transplant levels of circulating anticoagulants has not been well studied. We analement, and the coagulation system. In the setting of acutely ill non-transplant patients, this has been termed the syslyzed 205 patients in an attempt to correlate organ dysfunction and AT and PC deficiencies with these temic inflammatory response syndrome. 3 This syndrome has been well described in patients with trauma or severe transplant-specific factors (78 BMT with GM-CSF after transplant, 95 PBSCT without GM-CSF after transinfection, 3-5 but is only recently been recognized in patients undergoing HSCT. plant, and 32 PBSCT with GM-CSF after transplant). Patients transplanted with PBSC had a lower incidenceMcDonald et al 1 showed that patients with hepatic venoocclusive disease were at a greater risk of subsequent muliof pulmonary dysfunction (20 vs 40%, P = 0.006) and liver dysfunction (4 vs 13%, P = 0.05) than patients organ failure and death than patients without this complication. In addition, we recently reported a series of 199 receiving BM. The use of GF after transplant did not influence the development of subsequent organ dysfuncpatients undergoing HSCT, in whom development of pulmonary or CNS dysfunction significantly increased the risk tion. In multivariate analysis, the stem cell source was again predictive of pulmonary dysfunction. In contrast, of subsequent development of other organ dysfunction and of death, compared with patients without these single organ although patients transplanted with PBSC also had a lower incidence of PC deficiency (50 vs 81%, P Ͻ 0.01) dysfunctions. 2 These observations are similar to the systemic inflammatory response syndrome seen in other severand AT deficiency (20 vs 54%, P Ͻ 0.01) as compared with patients receiving BM, use of GM-CSF after transely ill patients, and suggest that single organ failure in the post-HSCT setting may not be a disorder confined to one plant was a more significant risk factor for the development of a...
We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.
We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.
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