Summary:Bone marrow (BM) and/or peripheral blood progenitor cells (PBPC) given after high-dose chemo-radiotherapy are commonly cryopreserved. Re-infusion of the thawed product can cause cardiovascular and other complications. We compared two groups of adult patients receiving autologous BM or PBPC transplant to assess the incidence of adverse events occurring during infusion. Fifty-one patients received BM, and 75 PBPC. The two groups were comparable in respect of age, total volume infused, quantity of dimethylsulfoxide (DMSO) and number of polymorphonuclear neutrophils. Patients receiving PBPC had a higher number of nucleated cells per kg of body weight; those in the BM group received a significantly greater quantity of red cells. Non-cardiovascular complications occurred in 19% and 8% of patients rescued by BM and PBPC respectively. The incidence of hypertension was 21% in the BM and 36% in the PBPC group. Asymptomatic hypotension was more frequent in PBPC patients (P Ͻ 0.001). Bradyarrhythmia was noticed in two of 75 PBPC patients and in 14 of 51 BM patients (P Ͻ 0.001). In the former group one patient had heart block; he died of renal failure 10 days later. Bradycardia and hemoglobinuria were more common in patients receiving BM where a higher concentration of red cells was present (P Ͻ 0.001). Since bradyarrhythmias may be a life-threatening complication we advise continuous careful monitoring during infusion of thawed BM. The strong correlation between bradycardia and red blood cell contamination suggests the use of purified products with a very low red cell content.

BackgroundHuman cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants.

Summary:Sixty-five patients with hematological malignancies (25 multiple myeloma, 18 Hodgkin's disease, 22 non-Hodgkin's lymphomas) who received a carmustine-based regimen followed by autologous PBPC transplantation, were studied retrospectively to evaluate the incidence of post-transplant non-infective pulmonary complications (NIPCs), risk factors predictive of NIPCs, and response to steroids. Carmustine (BCNU) given i.v. at a dose of 600 mg/m 2 was combined with etoposide and cyclophosphamide in 40 patients (BCV regimen) and with etoposide and melphalan in 25 patients (BEM regimen). Seventeen of 65 patients (26%) had one episode of NIPCs. The median time to NIPCs was 90 days (52-289). Factors that increased the risk of developing NIPCs on multivariate analysis were female sex (P Ͻ 0.001) and BCV regimen (P Ͻ 0.05). All patients with NIPCs received prednisone at a dose of 1 mg/kg body weight for 10 days then tapered by 5 mg every two days; complete response to steroids was achieved in 15 of 17 patients; one unresponsive patient died of interstitial pneumonia. BCNU given at the dose of 600 mg/m 2 is well tolerated when associated with melphalan and etoposide. In females and in patients receiving BCNU with cyclophosphamide, a BCNU dose reduction may be advisable. Bone Marrow Transplantation (2000) 25, 309-313. Keywords: carmustine; pulmonary toxicity; autologous peripheral blood progenitor cell transplantation There is evidence that several agents used in the preparative regimens for both autologous and allogeneic bone marrow transplantation may induce lung injury without evidence of infection. Agents that have been implicated include carmustine (BCNU), busulphan, cyclophosphamide (CY), and total body irradiation.1 BCNU causes toxic lung reactions characterized by chronic interstitial fibrosis, cough, dyspnea and decrease in lung diffusing capacity; toxicity related to the use of BCNU is suspected to be caused by damage to the glutathione system.2 BCNU has been included in highdose conditioning regimens for gliomas, breast cancer, Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma. Toxic pulmonary reactions have been recognized in as many as 16-64% of patients; 3-13 onset generally occurs within 1 year of starting BCNU. Events occurring up to 17 years later have been reported.14 The drug seems to cause pulmonary damage in a dose-related manner: 5,10,11 Phillips et al 6 reported a 9.5% incidence of fatal pulmonary toxicity in patients receiving BCNU doses as high as 1.200 mg/m 2 as a single agent; another report suggests no pulmonary toxicity at doses of less than 1000 mg/m 2 . 7 The threshold dose for BCNU toxicity is still controversial: lung toxicity may occur at 600 mg/m 2 when the drug is associated with other toxic agents like CY. 1,15 This report deals with patients with hematological malignancies who received a carmustine-based preparative regimen; the drug was combined with cyclophosphamide and etoposide or with etoposide and melphalan and both regimens were followed by autologous peripheral blo...

A randomized trial comparing a DNAemia cutoff of 10 000 copies per ml whole blood and first pp65 antigenemia positivity for initiation of preemptive therapy of human cytomegalovirus (HCMV) infection in adult hematopoietic stem cell transplant recipients was completed. DNAemia was chosen for cutoff definition since it is more automatable and standardizable than antigenemia, and more closely reflects the actual viral replication. The primary end point of the study was to compare the number of patients treated in the two arms. A total of 83 patients (42 in the DNAemia, and 41 in the antigenemia arm) were enrolled in the study. The incidence of HCMV infection, as detected by the relevant randomization assay (76% in the DNAemia versus 85% in the antigenemia arm), was comparable in the two arms, whereas the number of patients treated was significantly lower in the DNAemia arm (63 versus 80%, P ¼ 0.02). A single patient in the DNAemia arm suffered from biopsy-proven HCMV gastric disease diagnosed in the absence of detectable virus in blood. The incidence of graft-versus-host disease, and transplantation-related mortality did not differ between the two arms. In conclusion, our study shows that the use of a cutoff significantly reduces the number of patients requiring antiviral treatment, thus sparing unnecessary drug administration.