Summary:Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m 2 ), and thiotepa (400 mg/m 2 ) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m 2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m 2 (0.61 ؎ 0.09 vs 0.67 ؎ 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 ؎ 0.05 vs 0.63 ؎ 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m 2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m 2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy. Bone Marrow Transplantation (2001) 27, 307-310. Keywords: ejection fraction; cardiac toxicity; cyclophospamide; anthracycline; BMT High-dose cyclophosphamide (CY) used in transplant conditioning can induce cardiac toxicity. It occurs most com- monly after doses of 180 mg/kg or more, and signs and symptoms of congestive heart failure (CHF) occur within the initial 2 or 3 weeks after hematological stem cell transplantation (HCT). 1,2 Many patients receive anthracycline antibiotics, which impair cardiac function in a dose-dependent manner. 3 It is unclear whether anthracycline given prior to a transplant increases the risk of CY-induced cardiac toxicity and whether the occurrence of cardiac toxicity is correlated with a reduction in left ventricular ejection fraction (EF) before HCT. One clinical study showed that a reduced EF but cumulative pretransplant anthracycline dose has a tendency to provoke severe cardiac toxicity. 4 Others observed that severe cardiac toxicity is not predicted by EF value before HCT. 5 In these studies, a variety of preparative regimens was used, and some regimens did not contain CY, which was shown to be a significant risk factor for the development of cardiac toxicity. 6 These factors make it impossible to assess whether cardiac toxicity is directly influenced by the preparative regimen.We retrospectively analyzed the development of cardiac complications in patients who had undergone HCT with the same preparative regimen con...

Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study.

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.

Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study. Am.

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